High-throughput combinatorial screening identifies ...

High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell–like diffuse large B-cell lymphoma cells Lesley A. Mathews Grinera,1, Rajarshi Guhaa,1, Paul Shinna,1, Ryan M. Youngb,1, Jonathan M. Kellera, Dongbo Liua, Ian S. Goldlusta, Adam Yasgara, Crystal McKnighta, Matthew B. Boxera, Damien Y. Duveaua, Jian-Kang Jianga, Sam Michaela, Tim Mierzwaa, Wenwei Huanga, Martin J. Walsha, Bryan T. Motta, Paresma Patela,c, William Leistera, David J. Maloneya, Christopher A. Leclaira, Ganesha Raia, Ajit Jadhava, Brian D. Peyserd, Christopher P. Austina, Scott E. Martina, Anton Simeonova, Marc Ferrera, Louis M. Staudtb,2, and Craig J. Thomasa,2 a

Division of Preclinical Innovation, National Institutes of Health Chemical Genomics Center, National Center for Advancing Translational Sciences, Metabolism Branch, Center for Cancer Research, and dDevelopmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and cBasic Science Program, SAIC-Frederick, Inc., Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD 21702 b

The clinical development of drug combinations is typically achieved through trial-and-error or via insight gained through a detailed molecular understanding of dysregulated signaling pathways in a specific cancer type. Unbiased small-molecule combination (matrix) screening represents a high-throughput means to explore hundreds and even thousands of drug–drug pairs for potential investigation and translation. Here, we describe a high-throughput screening platform capable of testing compounds in pairwise matrix blocks for the rapid and systematic identification of synergistic, additive, and antagonistic drug combinations. We use this platform to define potential therapeutic combinations for the activated B-cell–like subtype (ABC) of diffuse large B-cell lymphoma (DLBCL). We identify drugs with synergy, additivity, and antagonism with the Bruton’s tyrosine kinase inhibitor ibrutinib, which targets the chronic active B-cell receptor signaling that characterizes ABC DLBCL. Ibrutinib interacted favorably with a wide range of compounds, including inhibitors of the PI3KAKT-mammalian target of rapamycin signaling cascade, other B-cell receptor pathway inhibitors, Bcl-2 family inhibitors, and several components of chemotherapy that is the standard of care for DLBCL. translational research

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(9). In normal B cells, BTK activity is required to transmit signaling from the B-cell receptor (BCR) to downstream pathways, notably NF-κB. Constitutive BCR signaling has been implicated in the pathogenesis of chronic lymphocytic leukemia, mantle cell lymphoma, and the activated B-cell–like subtype (ABC) of DLBCL. Oncogenic signaling in ABC DLBCL is initiated and reinforced by activating mutations affecting BCR subunits, as well as the signaling adapters CARD11 and MYD88, triggering constitutive activation of downstream NF-κB and JAK/STAT pathways that promote cancer cell survival and proliferation (10–12). ABC DLBCL cell lines are sensitive to inhibitors of various kinases (JAK, IKKβ, BTK, IRAK4), as well as agents that target key transcription factors that modulate their oncogenic signaling pathways, suggesting drug combinations that exhibit synergistic synthetic lethality for these lymphomas (13, 14). The BTK inhibitor ibrutinib has generated particular enthusiasm because of its ability to block BCR signaling in several B-cell malignancies (9). Ibrutinib is a highly targeted agent because of its Significance

| Imbruvica

The treatment of cancer is highly reliant on drug combinations. Next-generation, targeted therapeutics are demonstrating interesting single-agent activities in clinical trials; however, the discovery of companion drugs through iterative clinical trialand-error is not a tenable mechanism to prioritize clinically important combinations for these agents. Herein we describe the results of a large, high-throughput combination screen of the Bruton’s tyrosine kinase inhibitor ibrutinib versus a library of nearly 500 approved and investigational drugs. Multiple ibrutinib combinations were discovered through this study that can be prioritized for clinical examination.

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he standards of care for many diseases, including therapies for multiple types of cancer, involve drug combinations. Drug regimens can be comprised of as many as five or more agents, such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), which is commonly used for the treatment of diffuse large B-cell lymphoma (DLBCL) (1). Most of these regimens were the result of protracted, empirical clinical trial-and-error. With the advent of a wide repertoire of targeted agents in oncology and other areas of medicine, unbiased preclinical methods to discover and prioritize drug combinations are urgently needed (2, 3). Cancers use a diversity of pathological signaling and gene regulatory mechanisms to promote their survival, proliferation, and malignant phenotypes. Cancer gene sequencing across cancer cell line collections is a powerful means to identify genomic markers that may predict therapeutic response (4, 5). Targeted therapeutics have emerged as attractive strategies to block these dysregulated signaling events (6), but cancers use a variety of resistance mechanisms that must be addressed using rational drug combinations (7). The US Food and Drug Administration have indicated their willingness to consider combination of novel therapies at an earlier stage of clinical development (8), highlighting the need for innovative technologies to accelerate the discovery of novel drug combinations. In B-cell malignancies, Bruton’s tyrosine kinase (BTK) has emerged as a particularly interesting target for therapeutic attack

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Author contributions: L.A.M.G., R.G., P.S., A.S., M.F., L.M.S., and C.J.T. designed research; L.A.M.G., R.G., R.M.Y., J.M.K., D.L., I.S.G., A.Y., C.M., M.B.B., D.Y.D., J.-K.J., S.M., T.M., W.H., M.J.W., B.T.M., P.P., W.L., D.J.M., C.A.L., G.R., A.J., B.D.P., and C.J.T. performed research; L.A.M.G., R.G., P.S., R.M.Y., J.M.K., D.L., I.S.G., A.Y., C.M., M.B.B., D.Y.D., J.-K.J., S.M., T.M., W.H., M.J.W., B.T.M., P.P., W.L., D.J.M., C.A.L., G.R., A.J., B.D.P., C.P.A., S.E.M., A.S., M.F., L.M.S., and C.J.T. analyzed data; and L.A.M.G., R.G., P.S., I.S.G., A.S., M.F., L.M.S., and C.J.T. wrote the paper. The authors declare no conflict of interest. *This Direct Submission article had a prearranged editor. Data deposition: All single-agent data reported in this paper has been deposited in the PubChem database, http://pubchem.ncbi.nlm.nih.gov (summary AID 651556). 1

L.A.M.G., R.G., P.S. and R.M.Y. contributed equally to this work.

2

To whom correspondence may be addressed. E-mail: [email protected] or craigt@ mail.nih.gov.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. 1073/pnas.1311846111/-/DCSupplemental.

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Edited* by Ira Pastan, National Cancer Institute, National Institutes of Health, Bethesda, MD, and approved December 27, 2013 (received for review June 21, 2013)

ability to form a covalent bond with a conserved cysteine residue (C481) in the active site of BTK, resulting in remarkable selectivity and pharmacodynamics. Optimal clinical development of ibrutinib will likely depend upon its pairing with other agents to increase response rates and durability, as well as to circumvent potential ibrutinib-resistance mechanisms. Here, we describe a high-throughput combination screening platform on which a wide range of dosages for pairs of small molecules can be easily explored. We demonstrate the ability of this platform to identify agents that potentiate the toxicity of ibrutinib for cell line models of ABC DLBCL. The drug combinations discovered have both mechanistic and translational interest, including clinically actionable combinations of ibrutinib with PI3K pathway inhibitors and with chemotherapeutic agents that are part of the current standard of care for DLBCL. Results A High-Throughput Screening Platform for Identification of Drug– Drug Combinations. Various screening technologies and compu-

tational methods for the discovery of combination therapies have been reported (15–18). Challenges associated with establishing a combination screening platform include the building of an appropriate library of agents, the development of a robust plating system, and the establishment of a facile data interface. In this study, we evaluated 459 agents in combination with ibrutinib within 6 × 6 dose–response (matrix) blocks. The library, termed MIPE, was composed of oncology-focused, mechanistically annotated agents that were, as much as possible, prioritized for clinical relevance (Dataset S1). Mechanistic redundancy was embraced for selected target classes (e.g., the epidermal growth factor receptor family) because each agent may possess a unique polypharmacology that could yield distinctive activities in combination studies. To achieve customizable dose–response matrix blocks at a scale capable of interrogating thousands of drug–drug combinations, we used 1,536-well plate-enabled acoustic dispensers (19). Organization of each assay plate in true physical space resulted in 35 6 × 6 matrices within one 1,536-well plate. A single plate can be created in 15 min, affording full plating of this experiment in 3.5 h. The third primary requirement for this platform was a robust method for data analysis. Data were normalized to the plate positive control (bortezomib) and negative control (DMSO), such that the DMSO response was assigned a value of 100% and the bortezomib response was considered to be complete cell death and recorded as 0%. To avoid conflicting valuations in our analyses, we bounded all data

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to lie between 0% and 100%. Standard Z′-factor and minimum significant ratio metrics were used to assess interplate variability within this dataset (SI Appendix, Fig. S1). Plated wells were deconvoluted into individual response matrices and their combination behavior (additivity, synergy, antagonism) was characterized using a variety of metrics based on the Loewe, Bliss, and Gaddum models (see SI Appendix for detailed description of metrics) (20–23). Before combination analysis, we evaluated the single-agent activities of the MIPE library. The results from multiple singleagent profiles of the MIPE library suggested that a dose– response range between ∼10 nM and 2 μM would yield a range of active and inactive concentrations for the plurality of library members. Pilot combination experiments used 6 × 6 matrix block sizes, a starting concentration of 2.5 μM, and serial 1:4 dilutions of each agent. Confirmation studies with promising agents were conducted as 10 × 10 matrix blocks with customized starting concentrations and serial twofold dilutions. Comparative Analyses Associate Viability, Induction of Apoptosis, and NF-κB Responses. The single-agent responses of all 459 agents in

MIPE were generated using several cell-based assays, including cell viability (CellTiter-Glo), apoptosis (Caspase-Glo 3/7), and an NF-κB reporter assay (summary AID 651556) (Fig. 1A). Single-agent viability was assessed in two ABC DLBCL lines (TMD8 and HBL1). The MIPE library was also assayed for single-agent viability response in a bone marrow-derived human mesenchymal stem cell (hMSC) line to help gauge each agent’s potential therapeutic index. The ability of each agent to induce caspase 3/7 activation in TMD8 cells was examined at both 8- and 16-h time points to determine which agents induced an apoptotic response in a reasonable timeframe from a therapeutic exposure perspective. Given the reliance of ABC DLBCL cells on constitutive NF-κB signaling (9–11, 24–27), we tested the MIPE agents in a TNF-α–stimulated NF-κB–based β-lactamase reporter assay using an engineered ME-180 cervical carcinoma line (28). Representative dose–response curves from these various assays are shown in Fig. 1C for the cyclin-dependent kinase (CDK) inhibitor PHA-793887 (29). The data from these assays confirmed many known pharmacologic aspects of MIPE library agents, including ibrutinib, which exhibited single-agent toxicity below 100 nM for TMD8 cells, confirming previous results (10, 12). As expected for an oncology-focused library, many MIPE agents were toxic as single agents for TMD8 cells. Several classes of agents inhibited the transcriptional induction of the NF-κB reporter, including known

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○ = NF-B activation x = NF-B viability □ = hMSC cell viability ■ = TMD8 cell viability ▲= TMD8 apoptosis; 8 hrs Δ = TMD8 apoptosis; 16 hrs

Fig. 1. (A) Heatmap representation of MIPE library activity derived from qHTS of a previously reported (28) NF-κB assay in agonist (increased transcriptional response) and antagonist (decreased transcriptional response) mode and cell viability (percent cells remaining); control viability in hMSC, TMD8, and HBL1 lines; apoptotic response in TMD8 cells at 8 and 16 h. Red represents inhibitory response; green represents activation response; color intensity represents potency (stronger intensity means lower EC50 value). (B) Expansion of these data for selected agents of interest. (C) Complete response curves from these data sets for the CDK 1–5 inhibitor PHA-793887. [○, NF-κB activation; x, NF-κB viability; □, hMSC cell viability; ■, TMD8 cell viability; ▲, TMD8 apoptotic response (8 h); △, TMD8 apoptotic response (16 h)].

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Ibrutinib Combinations Involving PI3K Signaling Modulators. A striking number of cooperative interactions between ibrutinib and inhibitors of the PI3K signaling pathway were observed. Previous

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reports demonstrated that ABC DLBCL cells have constitutive PI3K signaling that supports their viability (10, 37). In the 6 × 6 discovery screen, 12 agents reported to inhibit various PI3K isoforms interacted favorably with ibrutinib (serials 102–113), including CAL-101 (idelalisib), BKM-120, and the dual PI3K/ mammalian target of rapamycin (mTOR) inhibitors BEZ-235 and GDC-0980 (38–41). The allosteric AKT inhibitor MK-2206 and the clinically approved mTORC1 inhibitor everolimus also demonstrated synergy at selected concentrations (42, 43). The chronic active BCR signaling in ABC DLBCL cells activates the kinase SYK, which is known to engage the PI3K pathway (10). Accordingly, the SYK inhibitor PRT-060318 (44) cooperated with ibrutinib in killing ABC DLBCL cells. Combinations of ibrutinib with various PI3K pathway inhibitors (MK-2206, CAL-101, BKM-120, BEZ-235, GDC-0941, GDC-0980, everolimus, PRT-060318) were confirmed to have synergistic/additive effects on ABC DLBCL viability in 10 × 10 matrix studies (http://tripod.nih.gov/matrix-data/btk-10x10-ctg-48hr/) (Fig. 2A and SI Appendix, Fig. S7). Representative results are shown for BKM120, a pan-class I PI3K inhibitor that is currently in phase II clinical trials (Fig. 2 A–D). One method of data visualization is a heat map indicating the degree of toxicity for each of the combinations in the 10 × 10 matrix (Fig. 2A). An isobologram representation shows that ibrutinib and BKM-120 cooperate in killing TMD8 cells in certain dose ranges of each drug (Fig. 2B and SI Appendix, Fig. S16). We conducted confirmatory MTS viability assays investigating the combination of ibrutinib with BKM-120 in several ABC DLBCL lines. Two methods were used to depict the cooperative effects of drug combinations. Data were normalized either to cells growing in the absence of either drug (Fig. 2C) or to the signal obtained with the specified concentration of ibrutinib alone (Fig. 2D). Left-curve shifts in the former method indicate superadditive effects of the combination. The BKM-120–ibrutinib

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NF-κB modulators and inhibitors of HSP90, the proteasome, and CDKs (Fig. 1B and SI Appendix, Figs. S2–S5) (30–32). In many cases, the mechanisms behind these effects are clear: HSP90 inhibitors reduce the activity of IκB kinase (IKK), the key regulatory kinase in the NF-κB pathway; proteasome inhibitors prevent the degradation of IκBα, a negative regulator of NF-κB; and panCDK inhibitors affect the NF-κB reporter by targeting CDK9, an integral component of the transcriptional elongation complex pTEFb. For some agents, such as withaferin A and CDDO-Me, the mechanistic basis for NF-κB blockade is less clear (Fig. 1C and SI Appendix, Fig. S6) (33, 34). The data from the 6 × 6 discovery screen of ibrutinib versus the MIPE library revealed many examples of synergy and additivity in ABC DLBCL viability assays (data are freely available at http://tripod.nih.gov/matrix-data/m3-btk-6x6-ls). Assignment of individual drug combinations as synergistic, additive, or antagonistic is governed by the model used (Excess HSA vs. Beta, for example). Here, we label combinations with a γ-value 0.5) at all ratios tested (Fig S16).

1. Smith T, et al. (2012) Comparison of compound administration methods in biochemical assays: effects on apperent compound potency using either assay-ready compound plates or pin tool-delivered compounds. J. Biomol. Screen. 18, 14-25. 2. Lehár J, Stockwell BR, Giaever G, Nislow C (2008) Combination chemical genetics. Nat. Chem. Biol. 4, 674-681. 3. Cokol M, et al. (2011) Systematic exploration of synergistic drug pairs. Mol. Sys. Biol. 7, 544. 4. Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enz. Regul. 22, 27-55. 5. Chou TC (2006) Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharm. Rev. 58, 621-681. 6. Chou TC (2010) Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70, 440-446.

Figure S1. Z’ factor for each 6X6 matrix plate and the distribution of the average IC 50 values for ibrutinib in each plate.

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Figure S2. Complete response curves from NFkB assay in agonist and antagonist mode and the cell viability control (PubChem AID 624478, 624479, 624476, respectively); viability as judged by celltiter-glo of the MIPE library agents in hMSC, TMD8 and HBL1 lines (PubChem AID 651696, 651645, 651646, respectively); apoptotic response as judged by caspase-glo of the MIPE library agents in TMD8 cells at 8 and 16 hours (PubChem AID 651713 and 651712, respectively) for selected CDK inhibitors. (○ = NF-κB antagonism; ● = NF-κB agonism; x = NF-κB viability; □ = hMSC cell viability; ■ = TMD8 cell viability; ▲= TMD8 apoptotic response (8 hours); Δ = TMD8 apoptotic response (16 hours).

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Figure S3. Complete response curves from NFkB assay in agonist and antagonist mode and the cell viability control (PubChem AID 624478, 624479, 624476, respectively); viability as judged by celltiter-glo of the MIPE library agents in hMSC, TMD8 and HBL1 lines (PubChem AID 651696, 651645, 651646, respectively); apoptotic response as judged by caspase-glo of the MIPE library agents in TMD8 cells at 8 and 16 hours (PubChem AID 651713 and 651712, respectively) for selected HSP90 inhibitors. (○ = NF-κB antagonism; ● = NF-κB agonism; x = NF-κB viability; □ = hMSC cell viability; ■ = TMD8 cell viability; ▲= TMD8 apoptotic response (8 hours); Δ = TMD8 apoptotic response (16 hours).

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antagonist mode and the cell viability control (PubChem AID 624478, 624479, 624476, respectively); viability as judged by celltiter-glo of the MIPE library agents in hMSC, TMD8 and HBL1 lines (PubChem AID 651696, 651645, 651646, respectively); apoptotic response as

judged by caspase-glo of the MIPE library agents in TMD8 cells at 8 and 16 hours (PubChem AID 651713 and 651712, respectively) for selected steroids. (○ = NF-κB antagonism; ● = NFκB agonism; x = NF-κB viability; □ = hMSC cell viability; ■ = TMD8 cell viability; ▲= TMD8 apoptotic response (8 hours); Δ = TMD8 apoptotic response (16 hours).

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Figure S5. Complete response curves from NFkB assay in agonist and antagonist mode and the cell viability control (PubChem AID 624478, 624479, 624476, respectively); viability as judged by celltiter-glo of the MIPE library agents in hMSC, TMD8 and HBL1 lines (PubChem AID 651696, 651645, 651646, respectively); apoptotic response as judged by caspase-glo of the MIPE library agents in TMD8 cells at 8 and 16 hours (PubChem AID 651713 and 651712, respectively) for selected proteasome inhibitors. (○ = NF-κB antagonism; ● = NF-κB agonism; x = NF-κB viability; □ = hMSC cell viability; ■ = TMD8 cell viability; ▲= TMD8 apoptotic response (8 hours); Δ = TMD8 apoptotic response (16 hours).

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Figure S6. Complete response curves from NFkB assay in agonist and antagonist mode and the cell viability control (PubChem AID 624478, 624479, 624476, respectively); viability as judged by celltiter-glo of the MIPE library agents in hMSC, TMD8 and HBL1 lines (PubChem AID 651696, 651645, 651646, respectively); apoptotic response as judged by caspase-glo of the MIPE library agents in TMD8 cells at 8 and 16 hours (PubChem AID 651713 and 651712, respectively) for selected inhibitors of IκB kinase (IKK) or NF-κB expression, activation or signaling. (○ = NF-κB antagonism; ● = NF-κB agonism; x = NF-κB viability; □ = hMSC cell viability; ■ = TMD8 cell viability; ▲= TMD8 apoptotic response (8 hours); Δ = TMD8 apoptotic response (16 hours).

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Figure S7. Selected Analysis of Ibrutinib + inhibitors of the PI3K signaling pathway. Matrix blocks representing 10×10 TMD8 viability data and single agent and combination responses informing on TMD8, OCI-Ly10, HBL1 and BJAB viability as judged by MTS response in 96 well-plates. *Curves indicate viability of cells treated with escalating doses of ibrutinib or selected agents alone at the concentrations indicated or combinations of selected agents at the concentrations indicated and a fixed sub-lethal dose of ibrutinib (0.5 nM or 1.0 nM).


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Figure S8. Selected Analysis of Ibrutinib + common chemotherapeutics. Matrix blocks representing 10×10 TMD8 viability data.

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Figure S9. Demonstration of data fidelity between 1536 and 384 well-plates. Matrix blocks representing 6×6 TMD8 viability data, 10×10 TMD8 viability data, 10×10 TMD8 viability data (384-well result) for selected ibrutinib+PI3K pathways modulating drug combinations displaying synergy or additivity.

Figure S10. Correlation assessment between the Excess HSA-versus-Beta for all combinations was performed.

Figure S11. Correlation assessment between the Excess HSA-versus-Gamma scoring values for all combinations was performed.

Figure S12. Correlation assessment between the Beta-versus-Gamma scoring values for all combinations was performed.

Figure S13. The 6×6 heatmap and isobolographic assessment for the synergistic drug combination of ibrutinib+CAL-101: Gamma value of 0.81.

Figure S14. The 6×6 heatmap and isobolographic assessment for the additive drug combination of ibrutinib+ixazomib: Gamma value of 0.99.

Figure S15. The 6×6 heatmap and isobolographic assessment for the antagonistic drug combination of ibrutinib+canertinib: Gamma value of 1.13.

Ibrutinib –vs–BKM-120 (Fig 2. data)

Ibrutinib –vs–BKM-120 (Isobologram. data) (bounded)

Ibrutinib –vs–BKM-120 (Isobologram. data) (unbounded)

Ibrutinib –vs– Dox (Fig 2. data)

Ibrutinib –vs– Dox (Isobologram. data) (bounded)

Ibrutinib –vs– Dox (Isobologram. data) (unbounded)

Normalized data for Fa plots for Ibrutinib –vs–BKM-120 (Isobologram data) 0.993 0.989 0.966 0.893 0.718 0.744 0.636 0.697 0.528 0.531 100

0.984 0.993 0.967 0.893 0.658 0.716 0.652 0.624 0.615 0.468 50

0.984 0.983 0.959 0.813 0.682 0.716 0.619 0.606 0.515 0.420 25

0.988 0.968 0.965 0.827 0.632 0.518 0.554 0.552 0.474 0.426 12.5

0.985 0.983 0.975 0.982 0.967 0.929 0.962 0.916 0.856 0.776 0.652 0.726 0.531 0.981 0.562 0.550 0.397 0.397 0.475 0.349 0.367 0.420 0.353 0.329 0.345 0.270 0.159 0.401 0.339 0.123 6.25 3.125 1.5625 Ibrutinib (nM)

0.976 0.927 0.849 0.550 0.152 0.303 0.362 0.336 0.093 0.057 0.781

0.968 0.93 0.689 0.480 0.405 0.304 0.280 0.239 0.130 0.154 0.390

0.967 0.905 0.665 0.525 0.284 0.353 0.242 0.280 0.159 0 0

2000 1000 500 250 125 62.5 31.25 15.62 7.812 0

BKM120 (nM)

Normalized data for Fa plots for Ibrutinib –vs–BKM-120 (Isobologram data) 0.9953 1.0059 0.9824 0.9597 0.8919 0.7752 0.6385 0.548 0.6374 0.5393 50

0.995 1.0089 0.9991 0.9921 0.8603 0.7709 0.7176 0.6398 0.5101 0.5822 28.571

0.9949 1.0054 0.9945 0.9879 0.8462 0.7925 0.721 0.5704 0.5362 0.4396 16.327

0.9955 1.0042 0.9996 0.9756 0.8551 0.8178 0.6943 0.5053 0.5658 0.5685 9.3294

0.9957 0.9909 1.0071 0.9931 0.993 0.959 0.9735 0.9338 0.734 0.8571 0.7295 0.6622 0.548 0.5007 0.6455 0.3585 0.5838 0.2924 0.5504 0.4789 5.3311 3.0463 Ibrutinib (nM)

0.87 0.9684 0.9654 0.889 0.6987 0.3585 0.4536 0.2723 0.2955 0.3296 1.7408

0.983 1.0029 0.9472 0.8931 0.6538 0.4396 0.3171 0.3051 0.1748 0.3571 0.9947

0.9858 0.9819 0.8814 0.7541 0.598 0.3764 0.3215 0.1526 0.0507 0.0139 0.5684

0.8653 0.911 0.7846 0.6304 0.3857 0.2345 0.036 0.0414 0.0312 0 0

100 57.143 32.653 18.659 10.662 6.0927 3.4815 1.9895 1.1368 0

Dox (nM)

Figure S16. Generation of Isobolograms and CI-Fa plots demonstrate synergy across range of ratios. Matrix blocks representing 10×10 TMD8 viability data from Figs 2B and 4B and those used to generate the isobolograms shown in Figs 2B and 4B (both bound and unbound data matrixes are shown as well as the normalized data for Fa plots). 100 nM Ibrutinib and 2000 nM BKM-120 were diluted 1:2 and 50 nM Ibrutinib and 100 nM Dox were diluted 1:1.75 (these dilutions provided averaged fixed ratio). Blue, red, green and orange arrows depict the averaged, fixed ratio data that was utilized in Figs 2B and 4B. Fa-CI plots are shown corresponding to the ratios used in Fig 2B and 4B. Multiple dose-ranging for these combinations can be found at https://tripod.nih.gov/matrix-client/rest/matrix/blocks/1171/table. Note; isobolographic analysis was performed from the unbounded data sets to allow CRCs possessing an increased data range.

NCGC ID

Name

Alias

Primary Mechanism

Additional Mechanisms

Phase

Structure

SMILES

Cl

COOH N

Cl

NCGC00181170

Bendamustine

Inno-P08001, SDX105, SyB L-0501 Antimetabolite

N

Approved O

HO

NCGC00015609

Lonidamine

AF-1890/KN228/TH-070

CN1C2=CC=C(N(CCCl)CCCl)C=C2N =C1CCCC(O)=O.Cl 3543-75-7

N

DNA Alkylating agnet

N Cl N

hexokinase inactivator

CAS #

HCl

Cl

Approved

ClC1=CC=C(C(Cl)=C1)CN2N=C(C(O) =O)C3=C2C=CC=C3 50264-69-2

NH2 N

NCGC00167491

Lenalidomide

O NH

Revlimid, CC5013, ENMD-0997 TNF-alpha Production Inhibitor

O=C1C2=CC=CC(N)=C2CN1C3CCC( NC3=O)=O 191732-72-6

O

O

Approved

Cl

NCGC00022567

NCGC00182045

Cladribine

Pentostatin

N

Leustat, 2-CdA, NSC-105014, RWJ-26251, RWJ26251-000 Adenosine Deaminase Inhibitor CI-825, CL67310465, NSC218321, PD81565, YK-176, Coforin, Nipent, Oncopent Adenosine Deaminase Inhibitor

N O

HO

Approved

NH2

N

H N N O

HO

OH

N

Approved

N

HO

SH

6-mercaptopurine

Purinethol, DR6MP

Purine Antagonist

N

N

Approved

OC[C@H]1O[C@@H](N2C(N=CNC[C @H]3O)=C3N=C2)C[C@@H]1O 53910-25-1

H N

N NCGC00091641

OC[C@H]1O[C@@H](N2C(N=C(Cl)N =C3N)=C3N=C2)C[C@@H]1O 4291-63-8

N

HO

SC1=NC=NC2=C1NC=N2.O

50-44-2

OCCO[C@@H]1CC[C@@H](C[C@H]([C@@ H]2CC([C@@H](C=C([C@H]([C@H](C([C@@ H](C[C@@H](C=CC=CC=C([C@H](C[C@@H] 3CC[C@H]([C@@](O3)(C(C(N4CCCC[C@H]4 C(O2)=O)=O)=O)O)C)OC)C)C)C)=O)OC)O)C) C)=O)C)C[C@H]1OC

159351-69-6

OH

O MeO

O

N

NCGC00242507

Everolimus

Afinitor, NVP-RAD001 mTOR inhibitor

O HO

O O

Rotamase (FKBP12) Inhibitor

O

O

OH O

MeO

OMe

Approved O H2N

NCGC00242510

Aminoglutethimide

Cytadren, AG-1

Aromatase Inhibitor

NH O

Approved

O=C(CCC1(CC)CC2=CC=C(N)C=C2) NC1=O 125-84-8

O H H

NCGC00015070

Formestane

4-OHA/CGP32349

Aromatase Inhibitor

OH

Approved NC

NCGC00016973

Letrozole

Femara, CGS20267, FEM-345

O=C1CC[C@@]2([H])[C@]3([H])CCC 4=C(O)C(CC[C@]4(C)[C@@]3([H])C C[C@@]21C)=O 566-48-3

H

O

CN

N

Aromatase Inhibitor

Approved

N N

N#CC(C=C1)=CC=C1C(C2=CC=C(C #N)C=C2)N3N=CN=C3 112809-51-5

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N

NCGC00242485

Pemetrexed disodium

Alimta, LY231514

thymidylate synthase inhibitor

dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase inhibitor

H2N

H N

N H

N H

O O-

O

Approved

O

Na+

O- Na+

C1=CC(=CC=C1CCC2=CNC3=C2C(= O)N=C(N3)N)C(=O)N[C@@H](CCC(= O)O)C(=O)O 150399-23-8

NH2 N HO

NCGC00168784

Gemcitabine

Gemzar, InnoD07001

ribonucleotide reductase inhibitor

N O F

Approved

Tamoxifen

ICI-46474

Selective Estrogen Receptor Modulators (SERM)

CN(C)CCOC(C=C1)=CC=C1/C(C2=C C=CC=C2)=C(CC)\C3=CC=CC=C3 10540-29-1

Protein Kinase C (PKC) Inhibitor Approved OH

H2SO4

N

N O

Vincristine sulfate

Oncovin, NSC67574

[H][C@]12[C@]3(CC)[C@@H](OC(C)=O)[C@] (C(OC)=O)(O)[C@]4([H])N(C=O)C5=CC(OC)= C([C@@](C6=C(CC7)C8=CC=CC=C8N6)(C(O C)=O)CC9CN7CC(O)(CC)C9)C=C5[C@@]41 CCN2CC=C3.O=S(O)(O)=O

H

OH

MeO

Tubulin polymerization inhibitor

95058-81-4

O

N H O

NCGC00242508

F[C@@]1(F)[C@H](O)[C@@H](CO) O[C@H]1N2C(N=C(N)C=C2)=O

OH F

N

NCGC00024928

O

N O

Approved

OAc

H O

O

2068-78-2

MeO MeO OMe

NCGC00263098

Combretastatin A-4


OH OMe

Phase III

OC1=CC(\C=C/C2=CC(OC)=C(OC)C( OC)=C2)=CC=C1OC 117048-59-6

O NH

N NH

HN

NCGC00263169

Plinabulin


HO

O O

NCGC00242509

Docetaxel

Taxotere, ANX514, RP-56976, NSC-628503

O=C(/C(NC/1=O)=C/C2=CC=CC=C2) NC1=C/C3=C(C(C)(C)C)NC=N3 714272-27-2

O

Phase II NH

O

H O OAc

O OH O

OH

Tubulin depolymerization inhibitor

OH

O

Approved

O

C[C@@]1(C)C2=C(C)[C@@H](OC([C@H](O)[ C@@H](NC(OC(C)(C)C)=O)C3=CC=CC=C3)= O)C[C@@]1(O)[C@@H](OC(C4=CC=CC=C4) =O)[C@@]([C@@]5(OC(C)=O)[C@H](OC5)C[ C@@H]6O)([H])[C@]6(C)C([C@@H]2O)=O

114977-28-5

O HO N N

NCGC00025281

Blebbistatin

myosin II ATPase inhibitor

O=C1C2(O)C(N(C3=CC=CC=C3)CC2 )=NC4=CC=C(C)C=C41 674289-55-5

Preclinical NH2

O

O=C1N(CC2=CC=CC=C2)C([C@H](N (CCCN)C(C3=CC=C(C)C=C3)=O)[C @H](C)C)=NC4=CC(Cl)=CC=C41 336113-53-2

N

NCGC00263174

Ispinesib

CK-0238273/SB715992

Kinesin-Like Spindle Protein Inhibitor

N

N

Cl

Phase II

O HO

O

H2N

HCl O

OH

O

OH OH

O

HO

NCGC00024415

Doxorubicin

Adriamycin

Topo II inhibitor

Approved

O

O

O=C1C2=C(O)C([C@@H](O[C@@H]3O[ C@@H](C)[C@@H](O)[C@@H](N)C3)C[ C@@](C(CO)=O)(O)C4)=C4C(O)=C2C(C 5=C1C(OC)=CC=C5)=O.Cl 25316-40-9

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES N HO

Nogitecan hydrochloride/NS C-609699

NCGC00014925

Topotecan hydrochloride

NCGC00015209

Clafen, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, Cyclophosphamide Cytophosphane

O

N

O=C1C2=C([C@@](O)(CC)C(OC2)= O)C=C3C4=NC5=CC=C(O)C(CN(C)C )=C5C=C4CN31.Cl 119413-54-6

N O

DNA Topoisomerase I Inhibitors

CAS #

HCl

Approved

HO

O

Cl

BCL2/LGALS1 Expression Inhibitor

O P N N H O

Approved

Cl

ClCCN(P1(NCCCO1)=O)CCCl

50-18-0

O HO OH

N NCGC00090851

H2N

DNA Methyltransferase (DNMT) Inhibitor

5-Azacitidine

N O

O N

N O

NH

O

NH

HN

NCGC00161622

Actinomycin D

DNA-Directed RNA Polymerase Inhibitor

O

NH2

Approved

O

HO

HO

OH CH3 O

OH CH3

O O

NCGC00162423

Mithramycin

O

N H

O O

N

O

Dactinomycin, NSC-3053

OH CH3

O

Mithracin, Plicamycin, A2371, NSC-24559 Alcohol Dehydrogenase Inhibitor

HO

CH3 HO O

HO

O

OH

CH3 H3C O

OH

O

O O

Cl

Canadiol, JK1211, R-51211

cytochrome inhibitor

CH3 OH

N N

O

320-67-2

CC(C1NC([C@H]([C@H](OC(C(N(C(CN(C([C @@H]2CCCN2C1=O)=O)C)=O)C)C(C)C)=O)C )NC(C3=C4N=C5C(OC4=C(C=C3)C)=C(C(C(N )=C5C(N[C@H]6[C@H](OC(C(N(C(CN(C([C@ @H]7CCCN7C(C(C(C)C)NC6=O)=O)=O)C)=O )C)C(C)C)=O)C)=O)=O)C)=O)=O)C

50-76-0

CO[C@H](C([C@H]([C@H](O)C)O)=O)C([C@@H]1O[ C@@H](O2)C[C@@H]([C@H]([C@@H]2C)O)O[C@ @H](O3)C[C@@H]([C@H]([C@@H]3C)O)O[C@@H]( O4)C[C@](CO)([C@H]([C@@H]4C)O)O)CC5=C(C1= O)C(O)=C6C(C=C(C(C)=C6O)C[C@H](O7)C[C@@H]( [C@H]([C@H]7C)O)O[C@H](O8)C[C@H]([C@@H]([C @H]8C)O)O)=C5

18378-89-7

N O

O

Itraconazole

CH3 O OH

O

Approved Cl

NCGC00018268

O

N

O

O

N

N

O

O

N

O

OC[C@H]1O[C@@H](N2C=NC(N)=N

OH C2=O)[C@@H]([C@@H]1O)O

O

N

Approved

N

O

N

N

N N

Approved

CCC(N1N=CN(C2=CC=C(N3CCN(C4 =CC=C(C=C4)OCC5COC(O5)(C6=C C=C(C=C6Cl)Cl)CN7C=NC=N7)CC3) C=C2)C1=O)C 84625-61-6

OH

H2SO4 HN

N

Cl

NCGC00159483

NCGC00025179

Hydroxychloroquin e sulfate Plaquenil

Mifepristone

C-1073, CI-1073, RU-38486, RU486, VGX-410, VGX-410C, VX410

Autophagy Inhibitor

CCN(CCCC(NC1=CC=NC2=CC(Cl)= CC=C12)C)CCO.O=S(O)(O)=O 747-36-4

N

Approved N

Progesterone Receptor Antagonist

Androgen Receptor Ligand, Glucocorticoid Receptor Antagonist, Internal Ribosomal Entry Site Inhibitor

O H

Approved

O

NH

NH

NCGC00016564

Metformin HCl

ADX-155, La6023, SMP-862

AMP-Activated Protein Kinase (AMPK) Activator

HCl

NH2

N H

N

CC#C[C@@]1(CC[C@H]2[C@@H]3 CCC4=CC(CCC4=C3[C@@H](C5=C C=C(N(C)C)C=C5)C[C@]12C)=O)O 84371-65-3

Approved

CN(C)C(NC(N)=N)=N.Cl

1115-70-4

O N

H2N H2N

NCGC00165736

Acadesine

AICAR/AR100/SCH-900395


N O

HO

Phase II

HO

OH

O[C@H]1[C@@H](O)[C@H](N2C(N) =C(C(N)=O)N=C2)O[C@@H]1CO 2627-69-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

NC

CAS #

OH

O HN

NCGC00250373

NCGC00159456


A-769662

Imatinib

Gleevec, STI-571, GGP-57148B Bcr-Abl Inhibitor

HO

Preclinical Abl/BCRP; ABCG2)/CSF1R (cFMS)/KIT (CKIT)/PDGFRalpha/PDGFRbeta Inhibitor

OC1=C(C#N)C(NC2=C1C(C3=CC=C( C4=C(O)C=CC=C4)C=C3)=CS2)=O 844499-71-4

S

N

N H

N

Approved

N

O

H N

N

CS(=O)(O)=O.O=C(NC1=CC=C(C)C( NC2=NC=CC(C3=CC=CN=C3)=N2)= C1)C4=CC=C(CN5CCN(C)CC5)C=C4 152459-95-5

N CF3 O

H N

N

N H

N

N

N

CC(C=CC(C(NC1=CC(N2C=C(C)N=C 2)=CC(C(F)(F)F)=C1)=O)=C3)=C3NC 4=NC=CC(C5=CC=CN=C5)=N4 641571-10-0

CH3 N

NCGC00183285

Nilotinib

AMN-107

Bcr-Abl Kinase Inhibitor

Approved H N

N N

NCGC00263152

Ponatinib

FGFR Inhibitor

Bcr-Abl/VEGFR/FGFR/Tie2 Inhibitor

O

N N

CF3

N

Phase II N N

O HN

NCGC00263172

DCC-2036

Bcr-Abl Inhibitor

Lyn/VEGFR-2 inhibitor; Tie2 Receptor Inhibitor

O

HN F

N

Phase II

O HN

N

O=C(C1=CC(C#CC2=CN=C3N2N=C C=C3)=C(C)C=C1)NC4=CC=C(CN5C CN(C)CC5)C(C(F)(F)F)=C4 943319-70-8 CC(C)(C)C1=NN(C(NC(NC2=C(F)C= C(OC3=CC=NC(C(NC)=O)=C3)C=C2 )=O)=C1)C4=CC5=C(C=C4)N=CC=C 5 1020172-07-9

Cl N

N

N

NCGC00181129

Dasatinib

Sprycel, BMS354825

Bcr-Abl inhibitor

BTK/Src inhibitor

S

N H

N

HO

HN

N

Approved Cl

Cl

MeO MeO

NCGC00241107

Bosutinib

PF-5208763/SKI606

Bcr-Abl inhibitor

Abl/Src inhibitor; STAT-5 Inhibitor

N

Approved

NH

N

N O

cSRC inhibitor

H N

NCGC00242490

PD-166285

cSRC inhibitor

FGFR1, Myt1, Wee1 inhibitor

O

Cl

Phase II

N

O

HN

O

AZD-0530

N

N

O

CN(CC1)CCN1CCOC2=CC(OC3CCO CC3)=C(C(NC4=C(Cl)C=CC5=C4OC O5)=NC=N6)C6=C2 379231-04-6

Cl

N

O HCl

CN(CC1)CCN1CCCOC2=CC3=C(C= C2OC)C(NC4=C(Cl)C=C(Cl)C(OC)=C 4)=C(C#N)C=N3 380843-75-4

N

O

N

Saracatinib

N

N

O

N

NCGC00241099

O=C(C1=CN=C(NC2=NC(C)=NC(N3 CCN(CCO)CC3)=C2)S1)NC4=C(C)C =CC=C4Cl 302962-49-8

O

O=C1C(C2=C(Cl)C=CC=C2Cl)=CC3= CN=C(NC4=CC=C(OCCN(CC)CC)C= C4)N=C3N1C.Cl.Cl 212391-63-4

HCl Cl

Preclinical Br

NCGC00167513

Vandetanib

Caprelsa, Zactima, AZD6474, CH-331, ZD6474 EGFR (HER1; erbB1) Inhibitor

HN MeO

Abl, Flt3, KIT, RET, VEGFR1/2/3 Inhibitor

O N

Approved

N N

F

CN(CC1)CCC1COC2=C(OC)C=C3C( N=CN=C3NC4=C(F)C=C(Br)C=C4)= C2 443913-73-3

NCGC ID

NCGC00164574

Name

Alias

Erlotinib hydrochlorid

Tarceva, CP358774, NSC718781, OSI-774, RG-1415, Ro-508231 EGFR (HER1; erbB1) inhibitor

Primary Mechanism


Phase

Structure

SMILES HN O

O O

N

Approved N

N

N

O HN

O

Gefitinib

Iressa/ZD-1839

C#CC1=CC=CC(NC2=NC=NC3=CC( OCCOC)=C(OCCOC)C=C32)=C1.Cl 183319-69-9

N

O

MeO

NCGC00159455

EGFR (HER1; erbB1) inhibitor

Cl

O

Lapatinib


HER2 (erbB2) Inhibitor

Neratinib

HER2 (erbB2), HER4 (erbB4) inhibitor

O=S(CCNCC1=CC=C(C2=CC3=C(N C4=CC=C(OCC5=CC=CC(F)=C5)C(C l)=C4)N=CN=C3C=C2)O1)(C)=O 231277-92-2

N

Approved

O NH

Cl H N

N

HKI-272, PB-272, WAY-179272 EGFR (HER1; erbB1) inhibitor

O S O

O

N

N

NCGC00241101

NH

NH

Cl

NCGC00167507

ClC1=CC(NC2=NC=NC3=C2C=C(OC CCN4CCOCC4)C(OC)=C3)=CC=C1F 184475-35-2

F

Approved F

Tykerb, GW572016F

CAS #

HCl

O

N

CCOC1=CC2=C(C(NC3=CC=C(C(Cl) =C3)OCC4=CC=CC=N4)=C(C#N)C= N2)C=C1NC(/C=C/CN(C)C)=O 698387-09-6

N

O

Phase III F O

HN

HN

NCGC00182713

Canertinib

CI-1033


HER2 (erbB2), HER4 (erbB4) inhibitor

N

Cl N

FC(C=C1)=C(Cl)C=C1NC2=NC=NC3 =CC(OCCCN4CCOCC4)=C(NC(C=C) =O)C=C32 267243-28-7

N

O

O

Phase II F HN

H N N

N

O

AV-412

MP-412



C=CC(NC1=C(C#CC(C)(C)N2CCN(C )CC2)C=C(N=CN=C3NC4=CC(Cl)=C( F)C=C4)C3=C1)=O 451492-95-8

N

N

NCGC00263195

Cl

Phase I F

N

NCGC00263185

Dacomitinib

PF-00299804/PF299 EGFR (HER1; erbB1) inhibitor

HN

H N

O=C(/C=C/CN1CCCCC1)NC2=C(OC) C=C(N=CN=C3NC4=CC(Cl)=C(F)C= C4)C3=C2 1110813-31-4

N

O MeO

HER2/HER4 Inhibitor

Cl

N

Phase III O HN

O MeO

N N

N H N

NCGC00263101

CP-724714


Phase I

CC1=CC(NC2=NC=NC3=CC=C(/C=C /CNC(COC)=O)C=C32)=CC=C1OC4= CN=C(C)C=C4 383432-38-0

F

N O

NCGC00185000

Afatinib

BIBW-2992



HN

H N

Phase III

Cl N

O=C(/C=C/CN(C)C)NC1=C(O[C@H]2 CCOC2)C=C(N=CN=C3NC4=CC(Cl)= C(F)C=C4)C3=C1 439081-18-2

N

O

O

N

NH N

N

NCGC00263149

AEE-788


HER2 (erbB2)/VEGFR-2 (FLK1/KDR) Inhibitor

N

Phase II

N H

C[C@H](C1=CC=CC=C1)NC2=C3C( NC(C4=CC=C(CN5CCN(CC)CC5)C= C4)=C3)=NC=N2 497839-62-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

HO

SMILES HN

H N

O O

NCGC00263177

CUDC-101


HER2 Inhibitor; HDAC Inhibitor

CAS #

C#CC1=CC=CC(NC2=NC=NC3=CC( OC)=C(OCCCCCCC(NO)=O)C=C32) =C1 1012054-59-9

N

MeO

N

Phase I F

H N

N

NCGC00263103

Pelitinib

EKB-569/WAYEKB-569

HN

O EtO

EGFR (HER1; erbB1) Inhibitor

N

Cl

FC(C=C1)=C(Cl)C=C1NC2=C(C#N)C =NC3=CC(OCC)=C(NC(/C=C/CN(C)C )=O)C=C32 257933-82-7

N

Phase II N N

OMe

NCGC00263144

WZ-4002

EGFR (HER1; erbB1) Inhibitor

N

ABT-869/RG-3635 VEGFR-2 inhibitor

ClC1=CN=C(NC2=CC=C(N3CCN(C) CC3)C=C2OC)N=C1OC4=CC(NC(C= C)=O)=CC=C4 123269-23-6

F

O

Linifanib

O N H

O

Preclinical HN

NCGC00250403

Cl

N N H

CSF1R Inhibitor/ERK,Flt3, PDGFRbeta inhibitor; PARP Inhibitor/STAT-5 Inhibitor

N H

NH2

O=C(NC1=CC(C)=CC=C1F)NC(C=C2 )=CC=C2C3=C4C(NN=C4N)=CC=C3 796967-16-3

N N H

Phase III

N

O=C(NC)C1=C(SC2=CC(NN=C3/C=C /C4=CC=CC=N4)=C3C=C2)C=CC=C 1 319460-85-0

N

NCGC00241108

Axitinib

Inlyta, AG-013736, AG-13736 VEGFR-1/2/3 Inhibitor

N H

S

PDGFR Inhibitor

N H

Phase III

O

O OH S O

Cl

NCGC00167488

Sorafenib

Nexavar, BAY-430006, BAY-549085 VEGFR-1/2/3 Inhibitor

HN

F3C

O

NH

Flt3, KIT, PDGFRbeta, RET, Raf kinase B, Raf kinase C Inhibitor Approved

O N

N H

O

O=C(NC1=CC=C(Cl)C(C(F)(F)F)=C1) NC2=CC=C(OC3=CC=NC(C(NC)=O) =C3)C=C2.O=S(C4=CC=C(C)C=C4)( O)=O 475207-59-1

Cl HCl

NCGC00181350

Vatalanib

CGP-79787D, PTK-787, PTK/ZK, ZK-222584 VEGF inhibitor

HCl

N

Aromatase/KIT (CKIT)/PDGFRbeta inhibitor

N

N

NH

ClC1=CC=C(C=C1)NC2=NN=C(C3=C 2C=CC=C3)CC4=CC=NC=C4.Cl.Cl 212141-51-0

Phase III O

NCGC00263205

Motesanib

AMG-706

VEGFR-1,2,3 Inhibitor

KIT/PDGFR Inhibitor

N H

N H NH

N

O=C(NC1=CC(NCC2(C)C)=C2C=C1) C3=CC=CN=C3NCC4=CC=NC=C4 857876-30-3

N

Phase III Cl

H N

H N O

O

N O

ClC1=CC(OC2=CC=NC3=CC(OC)=C (OC)C=C32)=CC=C1NC(NC4=NOC( C)=C4)=O 475108-18-0

MeO

NCGC00249390

Tivozanib

ASP-4130/AV951/KRN-951

MeO

VEGFR-1/2/3 Inhibitor

N

Phase III O N N

NH

NCGC00263156

Vargatef

Intedanib/BIBF1120


FGFR1/FGFR3/PDGFRalpha/P DGFRbeta Inhibitor

O

O

Phase III

O

N H

N

O=C(OC)C1=CC=C2C(NC(/C2=C(NC 3=CC=C(N(C(CN4CCN(C)CC4)=O)C) C=C3)/C5=CC=CC=C5)=O)=C1 928326-83-4

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

H N O

HO

N

O

NCGC00263160

Brivanib

BMS-540215

VEGFR-2,3/FGFR1,2,3 Inhibitor

N

CC(C(OC[C@@H](C)O)=C1)=C2N1N =CN=C2OC3=C(F)C(C=C(C)N4)=C4 C=C3 649735-46-6

F

N

VEGFR-2,3/FGFR1,2,3 Inhibitor Phase II

Cl

NH O O

O=C(NC)C1=CC(COC2=NN=C(NC3= CC=C(Cl)C=C3)C4=C2OC=C4)=CC= N1 332012-40-5

N

NCGC00249392

Telatinib

BAY-579352/BAY 57-9352 VEGFR-2,3 Inhibitor

NH

O N N

KIT/PDGFRbeta Inhibitor

Phase II H N

H N O

O

O

F

O=C(NC1=CC=C(F)C=C1)C2(CC2)C( NC(C=C3)=CC=C3OC4=CC=NC5=C C(OC)=C(OC)C=C54)=O 1140909-48-3

MeO

NCGC00263164

Cabozantinib

BMS-907351/XL184

VEGFR-2 Inhibitor

Flt3/HGFR/KIT/RET/ inhibitor, Tie2 Receptor Inhibitor

MeO

N

Phase III H N O MeO N

NCGC00263097

Cediranib

VEGFR-1/2/3 inhibitor

F

N

FC(C(C=C(C)N1)=C1C=C2)=C2OC3= NC=NC4=CC(OCCCN5CCCC5)=C(O C)C=C43 288383-20-0

N

O

Phase III H N N H2N

NCGC00263176

BMS-794833

VEGFR-2 Inhibitor

HGFR Inhibitor

H N

F

O

O

O

F

Cl

Preclinical

H N

NCGC00263198

Lenvatinib

E-7080/ER203492-00

O

O

MeO

N

Phase III

Cl

CP-547632

VEGFR-2 Inhibitor

EGFR/PDGFR Inhibitor

Foretinib

F

Phase II F

NCGC00263104

Br O

S N

O

EXEL-2880/GSK089/GSK1363089/XL-880 VEGFR-2 Inhibitor

O

H N O

OSI-632

O=C(N)C1=C(OC)C=C(N=CC=C2OC 3=CC(Cl)=C(NC(NC4CC4)=O)C=C3) C2=C1 417716-92-8 F

H2N

H N

N

NCGC00263100

H N O

H2N


H N

N

O

F

N

O

NC(C1=C(NC(NCCCCN2CCCC2)=O) SN=C1OCC3=C(F)C=C(Br)C=C3F)= O 252003-65-9

H N O

MeO

O

HGFR Inhibitor

FC1=C(OC2=CC=NC(N)=C2Cl)C=CC (NC(C3=CNC=C(C4=CC=C(F)C=C4) C3=O)=O)=C1 1174046-72-0

Phase II

FC1=CC(NC(C2(CC2)C(NC3=CC=C( F)C=C3)=O)=O)=CC=C1OC4=CC=N C5=C4C=C(OC)C(OCCCN6CCOCC6 )=C5 849217-64-7

O Cl

O

F3C

NCGC00263138

Regorafenib

BAY-73-4506

VEGFR-2 Inhibitor

N H

p38 MAPK/KIT/PDGFR/RET/Raf Inhibitor/Tie2 Receptor Inhibitor Phase III

H N

F

O

N H

N

N H

O N

NCGC00249685

Dovitinib

CHIR-258/NVPTKI258/TKI-258

F

FGFR inhibitor

Phase III

ClC1=C(C(F)(F)F)C=C(NC(NC2=CC= C(OC3=CC=NC(C(NC)=O)=C3)C=C2 F)=O)C=C1 755037-03-7

NH2 HN

N

N

O=C1C(C2=NC3=C(C=CC(N4CCN(C )CC4)=C3)N2)=C(N)C5=C(F)C=CC= C5N1 852433-84-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES H N

S

H N

N

N

O

O=C(C1=CC=C(CN2CCN(C)CC2)C= C1)NC3=CC=C(C)C(NC4=NC(C5=C C=CN=C5)=CS4)=C3 790299-79-5

N

NCGC00241103

Masitinib

AB-1010

FGFR 3 Inhibitor

KIT/Lyn Kinase Inhibitor

Phase III H N

O H N

N

N

N

NH

N

NCGC00165863

PD-173074

PD-0173074

FGFR 1/3 inhibitor

CAS #

N

OMe

OMe

Preclinical

CCN(CC)CCCCNC1=NC=C(C=C(C2 =CC(OC)=CC(OC)=C2)C(NC(NC(C)( C)C)=O)=N3)C3=N1 219580-11-7

OH

MeO

NCGC00263125

SG-00529

Palomid-529

Basic Fibroblast Growth Factor (bFGF; FGF2) Inhibitor

mTOR/Akt/VEGFR/mTORC1/mT ORC2 Inhibitor Phase II

O

O=C1OC2=CC(OCC3=CC=C(OC)C= C3)=C(OC)C=C2C4=C1C=C(C(C)O) C=C4 914913-88-5

O

O

MeO O H N

S

O

N

NCGC00263158

Amuvatinib

MP-470/HPK-56

PDGFRalpha Inhibitor

RET/AXL/Flt3/HGFR/KIT inhibitor, RAD51 Expression Inhibitor

S=C(NCC1=CC(OCO2)=C2C=C1)N( CC3)CCN3C4=NC=NC5=C4OC6=C5 C=CC=C6 850879-09-3

N O

N N

Phase II NH

O

OCF3

N N H

S

NCGC00263159

OSI-930

PDGFRbeta inhibitor

VEGFR-2/KIT inhibitor

Phase I Cl

NCGC00250400

Crizotinib

Xalkori, PF02341066, PF2341066

Cl

HGFR (MET; c-Met) Inhibitor

ALK Inhibitor

N N

O

F

H2N

C[C@@H](OC1=C(N)N=CC(C2=CN( C3CCNCC3)N=C2)=C1)C4=C(Cl)C(F )=CC=C4Cl 877399-52-5

Approved O

Cl

H N

S O O Cl

NCGC00242500

PHA-665752


NH

N

H N

O=C(NC1=CC=C(OC(F)(F)F)C=C1)C 2=C(C=CS2)NCC3=CC=NC4=C3C=C C=C4 728033-96-3

ClC1=CC=CC(Cl)=C1CS(C2=CC(/C( C(N3)=O)=C/C4=C(C)C(C(C5N(CN6 CCCC6)CCC5)=O)=C(C)N4)=C3C=C 2)(=O)=O 477575-56-7

N O

N

Preclinical O H N

F

N H2N

N O

O

O

F

Cl

NCGC00263157

BMS-777607


Phase II N

N

N

N

NC1=NC=CC(OC2=CC=C(NC(C3=C( OCC)C=CN(C4=CC=C(F)C=C4)C3= O)=O)C=C2F)=C1Cl 1196681-44-3

N N N

HO

NCGC00263161

PF-04217903


N

Discontinued

OCCN(N=C1)C=C1C2=CN=C3C(N(C C4=CC=C(N=CC=C5)C5=C4)N=N3)= N2 956906-93-7

N N N

NCGC00263189

JNJ-38877605


Phase I

N

N

N

F F

N

FC(C1=CC=C(N=CC=C2)C2=C1)(F)C 3=NN=C4N3N=C(C5=CN(C)N=C5)C= C4 943540-75-8

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

N N

NCGC00263163

SGX-523


S N

N

N

CN1N=CC(C(C=C2)=NN3C2=NN=C3 SC4=CC(C=CC=N5)=C5C=C4)=C1 1022150-57-7

N

Phase I

H N

N

O

N

F

F

O MeO N

NCGC00263201

AMG-51


KDR/Ron/IGFR inhibitor

Preclinical

CAS #

N

N

O

O

FC1=CC(C2=CN=C(NC3=CC=C(F)C =C3)N(C)C2=O)=CC=C1OC4=CC=N C5=CC(OCCCN6CCOCC6)=C(OC)C =C54 890019-63-3

OH O O O O

NCGC00022001

Picropodophyllin

AXL-1717/NSC36407

MeO

IGF-1R Inhibitors

Caspase 3 Activator

O[C@@H]1[C@@H]2[C@@H](C(OC 2)=O)[C@H](C3=CC(OC)=C(OC)C(O C)=C3)C4=CC5=C(OCO5)C=C41 477-47-4

OMe OMe

Phase II N

NH2

N N

NCGC00250375

Linsitinib

OSI-906/ASP7487

NC1=NC=CN2C1=C(C3=CC(N=C(C4 =CC=CC=C4)C=C5)=C5C=C3)N=C2[ C@@H]6C[C@@](O)(C)C6 867160-71-2

N

HO

IGF-1R Inhibitors

Phase III OMe O S N O

N

N

NH

N

N N

OMe N F

NH O F

NCGC00253439

GSK-1904529A

IGF-1R Inhibitor

Preclinical HCl

O

N

O=C(NC1=C(F)C=CC=C1F)C2=C(OC )C=CC(C3=C(C4=CC=NC(NC5=C(O C)C=C(N6CCC(N7CCN(S(=O)(C)=O) CC7)CC6)C(CC)=C5)=N4)N8C(C=CC =C8)=N3)=C2 1089283-49-7

N N N

HCl

NCGC00165869

Dorsomorphin

TGF-bR1 (ALK5) inhibitor

BMPR/AMPK inhibitor

N

Preclinical

C(C=N1)(C2=CC=C(OCCN3CCCCC3 )C=C2)=CN4C1=C(C5=CC=NC=C5)C =N4.Cl.Cl 1219168-18-9

O N

H2N

NCGC00249388

LY2157299

TGF-bR1 (ALK5) and TGFbR2 inhibitor

N

phase II

N

O

N

NC(C1=CC=C(C(C2=C(CCC3)N3N= C2C4=NC(C)=CC=C4)=CC=N5)C5=C 1)=O 700874-72-2

N

N

O

NCGC00242598

LY2109761

TGF-bR1 (ALK5) and TGFbR2 inhibitor

N

N N

Preclinical

C1(OCCN2CCOCC2)=CC=C(C(C3=C (CCC4)N4N=C3C5=NC=CC=C5)=CC =N6)C6=C1 700874-71-1

N

N N

S=C(NC1=CC=CC=C1)N(N=C2C3=N C(C)=CC=C3)C=C2C4=CC=NC5=CC =CC=C54 909910-43-6

N

HN S

NCGC00165721

A 83-01


ALK4, ALK7 inhibitor

Preclinical N N

NCGC00242054

SJN 2511


Preclinical

H N N

N

CC1=NC(C2=NNC=C2C3=NC4=CC= CN=C4C=C3)=CC=C1 446859-33-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

N HN N

N

NCGC00165898

SD-208

TGF-bR1 (ALK5) Inhibitor

F

N

N

FC1=CC=C(Cl)C=C1C2=NC3=NC=C N=C3C(NC4=CC=NC=C4)=N2 627536-09-8

Cl

Preclinical N NH

Cl

O

N NH O

S

O

N

CC(C)S(C1=CC=CC=C1NC2=NC(NC 3=CC=C(N4CCC(N5CCN(C)CC5)CC 4)C=C3OC)=NC=C2Cl)(=O)=O 761439-42-3

N N

NCGC00238453

TAE-684

NVP-TAE684

ALK Inhibitor

Preclinical N N

NCGC00186024

SB-525334


Alk4 inhibitor

N N H

Preclinical N O

NCGC00025230

SB-431542

TGF-bR1 (ALK5) Inhibitor

ALK 4/7 inhibitor

CC(C)(C)C1=NC(C2=CC=CC(C)=N2) =C(N1)C3=CC=C(N=CC=N4)C4=C3 356559-20-1

N

H N

O

N

NH2

O

Preclinical

H N

O N

O

O=C(NC(C=C1)=CC=C1OC(C)C)N(C C2)CCN2C3=C(C=C(OC)C(OCCCN4 CCCCC4)=C5)C5=NC=N3 387867-13-2

N

NCGC00241097

Tandutinib

MLN-0518, CT53518

O

N

KIT inhibitor

N N

O

Phase II

O HCl

HCl

N

O

N

O=C(NC1=NOC(C(C)(C)C)=C1)NC2= CC=C(C3=CN4C(SC5=C4C=CC(OC CN6CCOCC6)=C5)=N3)C=C2.Cl.Cl 1132827-21-4

S N

O O N

NCGC00242493

Quizartinib

AC-220/ASP-2689 KIT inhibitor

RET, c-FMS, Flt3 inhibitor

N H

Phase II

N H

HN N Cl

N

O N H

N H

N

N F

NCGC00250381

AZ-23

Trk inhibitor

NC(C(C=C1)=CC=C1C2=NC(C3=CC( OCO4)=C4C=C3)=C(C5=CC=CC=N5 )N2)=O 301836-41-9

Preclinical

ClC1=C(NC2=NNC(OC(C)C)=C2)N= C(N[C@H](C3=CC=C(F)C=N3)C)N=C 1 915720-21-7

N N HN

N

C1(C2=C(N=CC(C3=CC=C(N4CCNC C4)C=C3)=C5)N5N=C2)=C(C=CC=C 6)C6=NC=C1 1062368-24-4

N N

NCGC00249389

LDN-193189

BMPR inhibitor

Preclinical

NH

O

N

NCGC00253909

PRT-060318

PRT-318

Syk Kinase inhibitor

NH2

Preclinical

N H

NC(C1=C(NC2=CC=CC(C)=C2)N=C( N[C@@H]3CCCC[C@@H]3N)N=C1) =O 1194961-19-7

NH2 N

OMe F

O

NCGC00182051

R406

NSC-742317

Syk Kinase inhibitor

IL-2/IL-6/TNF-alpha Production Inhibitor

O

Phase III

N H

N

N H

OMe

N N

N H

OMe

O=C1C(C)(C)OC2=C(N=C(NC3=NC( NC4=CC(OC)=C(OC)C(OC)=C4)=NC =C3F)C=C2)N1 841290-80-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

N+

O O P O-

SMILES

CAS #

CCCCCCCCCCCCCCCCCCOP([O])(OC1CC[N+](C)(CC1)C)=O

157716-52-4

O

NCGC00187909

Perifosine

D-21266/KRX0401/NSC-639966 PI3K kinase activator

PKB/Akt inhibitor

Phase III O S O N

O N N

S

CS(N(CC1)CCN1CC2=CC3=C(S2)C( N4CCOCC4)=NC(C5=CC=CC6=C5C =NN6)=N3)(=O)=O 957054-30-7

N NH

N N

NCGC00187482

GDC-0941

RG-7321

PI3K Inhibitor

Phase I N F

NCGC00250408

GSK 2126458

PI3Kalpha/beta/delta/gamma 2126458/GSK-458 Inhibitor

F

mTORC1/mTORC2 Inhibitor

N

N

MeO O O S N H

O=S(NC1=C(OC)N=CC(C2=CC=C(N =CC=C3C4=CN=NC=C4)C3=C2)=C1) (C5=C(F)C=C(F)C=C5)=O 1086062-66-9

N

Phase I O N N N

O=C1N(C2=CC=CC=C2C)C(CN3C=N C4=C3N=CN=C4N)=NC5=C1C(C)=C C=C5 371242-69-2

N

N N

NCGC00168114

IC-87114

PI3K inhibitor

H2N

Preclinical

N N MeO OMe

NCGC00238454

PIK-90

PI3K Inhibitor

O N H

N

O=C(C1=CN=CC=C1)NC2=NC3=C(O C)C(OC)=CC=C3C4=NCCN24 677338-12-4

N

Preclinical O N N

CF3

N

N

NCGC00262604

BKM-120

NVP-BKM-120

PI3Kalpha inhibitor

Phase II

H2N

F

NC(N=C1)=CC(C(F)(F)F)=C1C2=CC( N3CCOCC3)=NC(N4CCOCC4)=N2 944396-07-0

O

N

O N N

O=C1N(C2=CC=CC=C2)C([C@H](CC )NC3=C(N=CN4)C4=NC=N3)=NC5=C 1C(F)=CC=C5 870281-82-6

N

HN

N N

NCGC00262603

CAL-101

GS-1101

PI3Kdelta inhibitor

NH

Phase II

N

N

N

CC1=NC2=CN=C(C=CC(C#CC3=CN =CC=C3)=C4)C4=C2N1C5=CC=C(C( C)(C)C#N)C=C5 853910-02-8

N

NCGC00263088

BAG-956

PI3K/PDK1 Inhibitor

N

Preclinical

O N N

N

O

NH

C[C@@H](NC1=CC=CC=C1C(O)=O) C2=CC(C)=CN3C2=NC(N4CCOCC4) =CC3=O 1173900-33-8

O OH

NCGC00263154

AZD-6482

PI3Kbeta inhibitor

Discontinued O N N N F3C

NCGC00263223

CAY10626

PI3Kalpha inhibitor

mTOR kinase inhibitor

Preclinical

O

N

N

O N H

N H

N

O=C(NC1=CC=C(C(N(CCN(C)C)C)= O)C=C1)NC(C=C2)=CC=C2C3=NC4= C(C=CN4CC(F)(F)F)C(N5CCOCC5)= N3 1202884-94-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N O

N

N

OH

N

NCGC00187906

PI-103

PI3Kalpha, beta, gamma Inhibitor mTOR; FRAP1 Inhibitor

OC1=CC(C2=NC3=C(OC4=C3C=CC =N4)C(N5CCOCC5)=N2)=CC=C1 677338-12-4

Preclinical O OH O

O O

NCGC00016094

NCGC00025288

17β-hydroxy Wortmannin

O

Deguelin

PI3K Inhibitor

Preclinical

PI3K Inhibitor

PKB/Akt/Cyclooxygenase-2 Inhibitor/NADH-Ubiquinone Oxidoreductase (Complex I)/NFkappaB (NFKB) Activation Inhibitor Preclinical

COC[C@H]1OC(C2=COC3=C2[C@ @]1(C)C([C@@H](C[C@@]4([C@H]( CC[C@@]54[H])O)C)OC(C)=O)=C5C 3=O)=O 58053-83-1

H O O

H O

O MeO H O

MeO

CC(C=C1)(C)OC2=C1C(O3)=C(C=C2 )C([C@@]([C@@]3([H])CO4)([H])C5= C4C=C(OC)C(OC)=C5)=O 522-17-8

O

HCl NH2 N

NC1(CCC1)C(C=C2)=CC=C2C3=NC 4=C(C=C3C5=CC=CC=C5)C(N6C=C 4)=NNC6=O.Cl.Cl 1032350-13-2

HCl

N

O

HN N

NCGC00186465

MK-2206

NSC-749607

AKT Inhibitor

phase II N O

N

NH2

NCGC00263147

A-674563

Akt1/PKA Inhibitor

N H

Preclinical

N[C@@H](CC1=CC=CC=C1)COC2= CN=CC(C3=CC=C(NN=C4C)C4=C3) =C2 552325-73-2

OH

H2N

NCGC00263181

GSK-690693

Akt1/2/3 Inhibitor

N

N

H N

CC(C)(O)C#CC1=C2C(N(CC)C(C3=N ON=C3N)=N2)=C(OC[C@@H]4CNC CC4)C=N1 937174-76-0

N N O

N O

Phase I

NC

O

N

N

CN(C(C=N1)=C(N2C3=CC=C(C(C)(C )C#N)C=C3)C4=C1C=CC(C5=CN=C6 C(C=CC=C6)=C5)=C4)C2=O 915019-65-7

N

NCGC00187481

BEZ235

NVP-BEZ-235

mTOR inhibitor

FRAP1, PI3K alpha, beta, gamma, delta inhibitor

N

Phase II O N

O N

NCGC00250398

PF-05212384

PKI-587

mTOR inhibitor

FRAP1/PI3Kalpha/PI3Kgamma Inhibitor

N

O

N

N H

N H

preclinical N S

N N

GDC-0980

R-7422/RG-7422

mTOR inhibitor

FRAP1/PI3K Inhibitor

O=C(NC1=NC(N2CCOCC2)=NC(N3C COCC3)=N1)NC4=CC=C(C(N5CCC( N(C)C)CC5)=O)C=C4 1197160-78-3

O

N

H2N

N O

O

NCGC00263109

N N

N

CC1=C(CN2CCN(C([C@@H](C)C)=O )CC2)SC3=C(N4CCOCC4)N=C(C5=C N=C(N)N=C5)N=C31 1032754-93-0

N N

Phase II O N

CF3 N N

NCGC00263215

Torin-1

mTOR inhibitor

PI3Kalpha Inhibitor

Preclinical

O N

N

O=C(N1C2=CC(C(F)(F)F)=C(N3CCN( C(CC)=O)CC3)C=C2)C=CC4=C1C5= CC(C6=CN=C(C=CC=C7)C7=C6)=C C=C5N=C4 1222998-36-8

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

CF3 O N

H2N

NCGC00263216

Torin-2

mTORC1 Inhibitor

N

O=C(N1C2=CC(C(F)(F)F)=CC=C2)C =CC3=C1C4=CC(C5=CN=C(N)C=C5) =CC=C4N=C3 1223001-51-1

N

Preclinical O N

OCC1=C(OC)C=CC(C2=CC=C3C(N= C(N4[C@@H](C)COCC4)N=C3N5[C @@H](C)COCC5)=N2)=C1 1009298-09-2

N HO

NCGC00250405

AZD-8055

mTORC1/2 Inhibitor

N

N

N

O

MeO

Phase II

OMe OH NH N

NCGC00250395

OSI-027

mTORC1/2 Inhibitor

O

O=C(O)[C@@H](CC1)CC[C@H]1C2 =NC(C3=CC4=C(C(OC)=CC=C4)N3) =C5N2N=CN=C5N 936890-98-1

N N

H2N N

Phase II

O N N HO

N

O

MeO

NCGC00250396

KU-0063794

mTORC1/2 Inhibitor

OCC1=C(OC)C=CC(C2=CC=C3C(N= C(N4C[C@@H](C)O[C@@H](C)C4)N =C3N5CCOCC5)=N2)=C1 938440-64-3

N

N

preclinical O N N

N N

N

NCGC00242484

WYE-354

mTORC1/2 inhibitor

O

Preclinical

O=C(OC)NC1=CC=C(C2=NC(N(C3C CN(C(OC)=O)CC3)N=C4)=C4C(N5C COCC5)=N2)C=C1 1062169-56-5

O N H

N

O

O

OH

O S

NCGC00015448

Salirasib

KD-032/ONO7056

mTOR Inhibitor

O=C(O)C1=CC=CC=C1SC/C=C(C)/C C/C=C(C)/CC/C=C(C)/C 162520-00-5

FRAP1 Inhibitor/TRPA1 Agonist Phase II O

N

O

NCGC00250377

NU-7441

DNA-Dependent Protein Kinase (DNA-PK) Inhibitor

O=C1C=C(N2CCOCC2)OC(C1=CC= C3)=C3C4=CC=CC5=C4SC6=C5C=C C=C6 503468-95-9

O

S

Preclinical N

O

HCl

N

HN

O=C1C2=CC=CC(C3=CC=C(NC(CN4 CCN(CC)CC4)=O)C5=C3SC6=C5C= CC=C6)=C2OC(N7CCOCC7)=C1.Cl. Cl.Cl 881375-00-4

HCl HCl

S

NCGC00250387

KU 0060648

DNA-Dependent Protein Kinase (DNA-PK) Inhibitor

O

Preclinical

O N

O

N

N N

NCGC00092318

NSC 23766

Rac1-GEF inhibitor

N H

N H

N

Preclinical O S

F3C

NCGC00188866

Rac1 inhibitor

Preclinical

N

N O

O O

NCGC00188866

CC(CCCN(CC)CC)NC1=NC(NC2=CC =C3C(C(N)=CC(C)=N3)=C2)=CC(C)= N1 733767-34-5

NH2

O=C1C(OCCCCCSC2=CC=NC3=CC( C(F)(F)F)=CC=C32)=COC(CN4CCO CC4)=C1

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O F

NH2

N F

NCGC00249684

VX-702

KVK-702

p38 MAPK Inhibitor

N NH2 F

O

F

Phase II

NC(N(C1=NC(C2=C(F)C=C(F)C=C2) =C(C(N)=O)C=C1)C3=C(F)C=CC=C3 F)=O 745833-23-2

F

NH

NCGC00025035

SB-203580

p38 MAPK Inhibitor

SAP&Jun Kinase Inhibitor/Calcium Channel Activator

N

Phase II

Cl O

VX-745

p38 MAPK Inhibitor

F N

N

F

Phase II O

N

Doramapimod

BIBR-796

p38 MAPK Inhibitor

SAPK2 (p38beta) Inhibitor

O=C1N=CN(N=C(SC2=C(F)C=C(F)C =C2)C=C3)C3=C1C4=C(Cl)C=CC=C4 Cl 209410-46-8

S

O N

O

NCGC00241104

N H

N

N H

CC(C)(C)C1=NN(C2=CC=C(C)C=C2) C(NC(NC3=CC=C(OCCN4CCOCC4) C5=CC=CC=C53)=O)=C1 285983-48-4

Phase II O Br

F

H N

N O

O F

NCGC00263165

PH-797804

p38 MAPK Inhibitor

FC(C=C1)=CC=C1C2=C(N=C(C3=CC =C(S(C)=O)C=C3)N2)C4=CC=NC=C 4 152121-47-6

Cl

N

NCGC00241111

S O

N

Phase II

FC1=C(COC(C=C(C)N2C3=CC(C(NC )=O)=CC=C3C)=C(Br)C2=O)C=CC(F) =C1 586379-66-0

N

NCGC00241112

RWJ-67657

p38 MAPK Inhibitor

IL-1beta Production Inhibitor/TNF-alpha Production Inhibitor

OH

N

F

Phase I

N N N

Talmapimod

p38 MAPK Inhibitor

Phase II OH OH O S O O S O

NH2 O N

FMK-MEA

MAPKAP-K1 (RSK; p90Rsk) Inhibitor

FC1=CC=C(CN2[C@@H](C)CN(C(C 3=C(Cl)C=C(N(C)C=C4C(C(N(C)C)= O)=O)C4=C3)=O)[C@H](C)C2)C=C1 309913-83-5

N

Cl

N

NCGC00263239

O

O

O F

NCGC00263140

OCCC#CC1=NC(C2=CC=C(F)C=C2) =C(C3=CC=NC=C3)N1CCCC4=CC= CC=C4 215303-72-3

N

HN

N

F

O

Preclinical

NC1=C2C(N(CCCNCCOC)C(C(CF)= O)=C2C3=CC=C(C)C=C3)=NC=N1.O =S(C4=CC=C(C)C=C4)(O)=O.O=S(C 5=CC=C(C)C=C5)(O)=O

F HO

NCGC00263086

BI-D1870

MAPKAP-K1 (RSK; p90Rsk) Inhibitor

N

N

F

N H

N

NH

N

OC1=C(F)C=C(NC2=NC(N(CCC(C)C) C(C)C(N3C)=N)=C3C=N2)C=C1F 501437-28-1

Preclinical H2N

S

O

N O

HN O

NCGC00253463

NCGC00253463

Chk1/Chk2 inhibitor

Preclinical

H2N

NC(C1=C(NC(N)=O)C=C(C2=CC=C( CN3CCOCC3)C=C2)S1)=O 494772-86-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

F

Cl

N

N

NCGC00250384

NCGC00263238

PHA-408

Withaferin A

NSC-101088

IKK-beta Inhibitor

preclinical

Vimentin Inhibitor

NF-kappaB Activation Inhibitor/Acetylcholinesterase Inhibitor/Butyrylcholinesterase Inhibitor/Protein Kinase C (PKC) Inhibitor Preclinical

NCGC00186460

IKK-epsilon Inhibitor

Bardoxolone methyl

NF-kappaB signaling Inhibitor

PDK 1/TBK/NAK/T2K Inhibitor NF-kappaB activation/Nitric Oxide Production Inhibitor; Glutathione Reductase (NADPH)/Nuclear Factor, Erythroid Derived 2, Like 2 (Nrf2)/Heme Oxygenase

O O

HO

H

O

H H

H

I N H

N

N H

O N H

N

N H

IC1=C(NCCCNC(C2=CC=CS2)=O)N= C(NC3=CC(NC(N4CCCC4)=O)=CC= C3)N=C1 702675-74-9

N

preclinical O

H

N

O

CC1(C)C[C@H](C(OC)=O)C2CC[C@ @]([C@@]3([H])[C@]2([H])C1)(C)[C @]4(C)CC[C@@]5([H])C(C)(C)C(C(C #N)=C[C@]5(C)C4=CC3=O)=O 218600-53-4

OMe H

O

H

Phase III

O=C(C1=C(Cl)C=NC(N2CCN(C)CC2) =C1)NC3=CC=C(CCC4=C5N(C6=CC =C(F)C=C6)N=C4C(N)=O)C5=C3 503555-55-3 OCC1=C(C[C@H]([C@H]([C@@]2([H ])CC[C@@]3([H])[C@]4([H])C[C@H]5 O[C@]56[C@H](C=CC([C@@]6([C@ @]4([H])CC[C@]23C)C)=O)O)C)OC1 =O)C 5119-48-2

OH O

O

BX-795

NH2 O

O

S

NCGC00250386

N N

H N

N

O N

N

HCl

O=C(N1CCC(N2CCCC2)CC1)C(C=C 3)=CC=C3NC4=NC=CC(C5=CC(C=C C=C6)=C6S5)=N4.Cl 1186195-62-9

HN

NCGC00167767

N

IKK1, IKK-2, IKK complex inhibitor

IKK16

S

N

Preclinical F

Cl

N

N N

H N

N

NH2 O

O

HO OH

NCGC00263213

PF-184

IKK-2 (IKK-beta) Inhibitor

Preclinical

NC(C1=NN(C2=CC=C(F)C=C2)C3=C 1CCC4=CC=C(NC(C5=C(Cl)C=NC(N 6C[C@@](CO)(C)[C@@](CO)(C)C6) =C5)=O)C=C43)=O 1187460-81-6

CF3 OH

O N H

NCGC00165811

IMD-0354

IKK-2 Inhibitor Inhibitor

NF-kappaB Activation Inhibitor

Phase I

CF3

O=C(C1=C(O)C=CC(Cl)=C1)NC2=CC (C(F)(F)F)=CC(C(F)(F)F)=C2 978-62-1

Cl

N

Cl N NH

NCGC00165873

PS-1145

MLN-1145

IKK-2 (IKK-beta) Inhibitor

Preclinical

N H

O=C(NC1=C(NC2=C3C=CN=C2)C3= CC(Cl)=C1)C4=CC=CN=C4 431898-65-6

O N

Cl MeO O

NCGC00263021

MLN-120B

IKK beta inhibitor

Preclinical

NH

N H

N

O=C(C1=CC=CN=C1C)NC2=C(OC)C (Cl)=CC3=C2NC4=C3C=CN=C4 783348-36-7

O HN O

NCGC00169964

cycloheximide

U-4527

GSK-3beta Inhibitor

tau Protein Kinase I Inhibitor

Approved

OH O H

O=C(CC(C[C@@H](O)[C@]1([H])C[C @@H](C)C[C@H](C)C1=O)C2)NC2= O 66-81-9

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

NH N

N

Cl

NCGC00250379

CT-99021

CHIR 99021

GSK-3 inhibitor

H N

N H

N

N

Cl

CN

Preclinical H N

O

CC1=CNC(C2=C(C3=CC=C(Cl)C=C3 Cl)N=C(NCCNC4=CC=C(C#N)C=N4) N=C2)=N1 252917-06-9

O

Cl

O=C(N1)C(C2=CN(C)C3=C2C=CC=C 3)=C(C4=CC(Cl)=CC(Cl)=C4)C1=O 280744-09-4

N

NCGC00263194

SB-216763

GSK-3 inhibitor

Preclinical

Cl O O

N

HN

O

N

NCGC00161703

NF-kB/AP-1 activation inhibitor

O=C(C=CC1=O)N1NC2=NC(C3=CC= CS3)=NC4=CC=CC(OC)=C42 1348249-76-2

S

N

NCGC00161703

Preclinical MeO

O=C(N1CCC(C2=CC=CC(C(F)(F)F)= C2)CC1)[C@](C)(C#N)[C@H](C3=CC 884491-41-2 =CC=C3OC)C4=CC=CC5=CC=CC=C (diastereomeri 54 c mixture)

O N

NCGC00263019

WAY-204688

SIM-688

NF-kappaB Activation Inhibitor

Estrogen Receptor alpha/beta Ligand

CN

Phase I

N

HOOC

NCGC00090903

Sulfasalazine

Azulfidine

NFKB Activation Inhibitors

CF3

O O S N H

Approved

N

I

O

BX-795

IKBKE Inhibitor

NH2

Preclinical

S

NCGC00250386

O

H N

N N

NFkappaB-inducing kinase Inhibitor

NCGC00263020

OC1=C(C(O)=O)C=C(/N=N/C2=CC= C(S(NC3=NC=CC=C3)(=O)=O)C=C2) C=C1 599-79-1

HO

N

NCGC00263020

N

N

PDK/TBK1; NAK; T2K Inhibitor

N H

N H

N

O N H

N H

N

N

Preclinical

O

S O N

O

O

NCGC00229735

KU-60019

KU-0060019

ATM Kinase Inhibitor

IC1=C(NCCCNC(C2=CC=CS2)=O)N= C(NC3=CC(NC(N4CCCC4)=O)=CC= C3)N=C1 702675-74-9

H N

N O

CC(C)N1C=C(C2=CC=NC(NC3=C(C) C=CC(C(N)=O)=C3)=N2)C4=C1C=N C=C4 1221153-14-5

Preclinical

O=C(CN1C[C@H](C)O[C@H](C)C1)N C2=CC3=C(SC(C(C4=CC(C=C(N5CC OCC5)O4)=O)=CC=C6)=C6C3)C=C2 925701-49-1

S S O N

O

O

NCGC00263190

KU-0064

KU-55933


Preclinical

O=C(C=C(N1CCOCC1)O2)C=C2C3= CC=CC4C3SC5=CC=CC=C5S4 587871-26-9

N N H2N

N

MeO

NCGC00263099

CP-466722


Preclinical

MeO

N N

N

NC1=NC(C2=NC=CC=C2)=NN1C3=N C=NC4=CC(OC)=C(OC)C=C43 1080622-86-1

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure HN N

O O HN

O NH O

N N N

N H

O

N H

N N N

N

NH

NCGC00263236

SM-164

cIAP1/2 and XIAP inhibitor

Preclinical O O S

NCGC00263208

NCGC00016423

TW-37

Bcl-xL inhibitor/Mcl-1 inhibitor

(-)-Gossypol

Bcl-xL inhibitor

OH OH

Preclinical Growth Factor Modulator/Lipid Peroxidation Inhibitor/Mcl-1 Inhibitor/11beta-Hydroxysteroid Dehydrogenase (11beta-HSD) Inhibitor

OH OH

HO

OC1=C(C(C)C)C(C=C2C)=C(C(C=O) =C1O)C(O)=C2C3=C(O)C4=C(C=O) C(O)=C(O)C(C(C)C)=C4C=C3C 303-45-7

CHO

Phase II OMe OMe

N+

C[N+]1=CC2=C(C=CC(OC)=C2OC)C 3=C1C4=CC(OCO5)=C5C=C4C=C3.[ Cl-] 3895-92-9

O

NCGC00015225

MP-0922/NSC646662

Bcl-xL inhibitor

P2X7 Receptor Antagonist/PKC Inhibitor/Rho GTPase Inhibitor Preclinical

957135-43-2

OH

CHO OH HO

Cl-

Chelerythrine chloride

CAS #

O=S(C1=C(C(C)(C)C)C=CC=C1)(C2= CC=C(NC(C3=C(O)C(O)=C(O)C(CC4 =CC=CC=C4C(C)C)=C3)=O)C=C2)= O 877877-35-5

O N H HO

O

SMILES O=C([C@H](C)NC)N[C@H]1CCCC[C@@H]2 N([C@H](C(N[C@@H](C3=CC=CC=C3)C4=C N(CCCCC5=CC=C(CCCCN(N=N6)C=C6[C@ H](C7=CC=CC=C7)NC([C@H]8N9C([C@@H]( NC([C@H](C)NC)=O)CCCC[C@H]9CC8)=O)= O)C=C5)N=N4)=O)CC2)C1=O

O

N HN OMe

N H

NCGC00263166

Obatoclax

GX-015-070

Bcl-xL inhibitor

CC1=CC(C)=C(N1)/C=C2C(OC)=CC( C3=CC4=CC=CC=C4N3)=N/2 803712-79-0

Phase II O O N H

O=C(NS(C1=CC=C(N[C@@H](CSC2 =CC=CC=C2)CCN3CCOCC3)C(S(=O )(C(F)(F)F)=O)=C1)(=O)=O)C4=CC= C(N5CCN(CC6=C(C7=CC=C(Cl)C=C 7)CCC(C)(C)C6)CC5)C=C4 923564-51-6

O CF3 S O

O S

N

NH

N S

NCGC00188344

Navitoclax

ABT-263, RG7433

N O

Bcl-xL inhibitor

Cl

Phase II

Cl O

O=C(N1CC(NCC1)=O)N2[C@@H](C 3=CC=C(Cl)C=C3)[C@@H](C4=CC= C(Cl)C=C4)N=C2C5=CC=C(OC)C=C 5OC(C)C 548472-68-0

N OMe N O

Cl

NCGC00263124

Nutlin-3

HDM2/HDMX inhibitor

N

NH O

Preclinical

NH2 CONH2 H N

AcHN O

O N H

OH H N

O N H

O

NH HN H N

O Me

CONH2

O N H OH

CONH2 O H N

O

H N

N H

O Me

O

CONH2

NH

O H2N

Ac-SAH-p53-8

HDM2/HDMX inhibitor

O

O HN H N

O Me O

H2N

NCGC00263280

NH H N

N H Me

O

Preclinical

H N

N H

Me Me

O Me

O Me CONH2

O=C(N[C@@H](CO)C(N[C@@H](CCC(N)=O)C(N[C@@H](CCC (N)=O)C(N[C@@H]([C@@H](O)C)C(N[C@@H](CC1=CC=CC= C1)C(N[C@@](CCCCCC/C=C/CCC2)(C)C(N[C@@H](CC(N)=O) C(N[C@@H](CC(C)C)C(N[C@@H](CC3=CNC4=C3C=CC=C4)C (N[C@@H](C(N[C@H](C(N[C@@H](CC(C)C)C(N[C@]2(C)C(N[ C@@H](CCC(N)=O)C(N[C@@H](CC(N)=O)C(N)=O)=O)=O)=O) =O)CC(C)C)=O)CCCNC(N)=N)=O)=O)=O)=O)=O)=O)=O)=O)=O) [C@H](CCC(N)=O)NC(CCNC(C)=O)=O

932726-23-3

H N N H N

N H

NCGC00263171

Serdemetan

JNJ-26854165

MDM2 (hdm2) Inhibitor

C12=CC=CC=C1C(CCNC3=CC=C(N C4=CC=NC=C4)C=C3)=CN2 881202-45-5

Phase I N

NH

O

N

N

N

NCGC00014873

HLI-373989

HLI-373

MDM2 (hdm2) Inhibitor

Preclinical

O

O=C(C1=C(NCCCN(C)C)C2=C(N(C) C1=N3)C=CC=C2)N(C)C3=O

502137-98-6

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES O O

N

O

N

CC1=NN(C(/C1=C/C2=CC(Cl)=C(OC C(OC)=O)C(OCC)=C2)=O)C3=CC=C C=C3 431979-47-4

Cl O

NCGC00263212

SJ-172550

MDM4 (MDMX) Inhibitor

CAS #

O

Preclinical NH2

O

NH O

S HN

F

NCGC00242481

AZD-7762

Chk1/2 Inhibitor

NH

H N N

O

N N

O

NCGC00250401

PF-477736

Flavopiridol

Chk1 Inhibitor Alvocidib, HL-275, HMR-1275, L868275, MDL107826A, NSC649890 CDK1/2/4/6/7/9 Inhibitor

N H

N H

NH2

NCGC00263132

O

OH

Cl HO HO

O

OC1=CC(O)=C([C@H]2[C@@H](O)C N(C)CC2)C(OC(C3=CC=CC=C3Cl)= C4)=C1C4=O 146426-40-6

N

H N

N

N

N

Purvalanol B

CDK1/2/3/4/5 inhibitor

Dual-Specificity Tyrosine-(Y)Phosphorylation Regulated Kinase (DYRK) Inhibitor

NCGC00094374

Seliciclib

N

HOOC Cl

Preclinical N

PHA-690509

N

N

HO

N NH

CDK 1,2,5,7,9 Inhibitor

CC(C)N1C=NC2=C(NCC3=CC=CC= C3)N=C(N[C@@H](CO)CC)N=C21

Phase II H N

O

NCGC00263191

CC(C)N1C=NC2=C(NC3=CC=C(C(O) =O)C(Cl)=C3)N=C(N[C@H]([C@H](C) C)CO)N=C21 212844-54-7

NH

H N

(R)-Roscovitine, NSC-701554, CYC-202

O=C(NC1=CC2=C3C(NC(C4=CN(C) N=C4)=C3C=NNC2=O)=C1)[C@H](N )C5CCCCC5 952021-60-2

Discontinued Bcl-2 Inhibitor, Mcl-1 Inhibitor, Survivin Inhibitor, XChromosome-Linked Inhibitor of Apoptosis Protein (XIAP) Inhibitor Phase III

HO

NCGC00025220

NC(NC1=C(C(N[C@H]2CCCNC2)=O) SC(C3=CC(F)=CC=C3)=C1)=O 860352-01-8

Discontinued

CDK2/Cyclin A Inhibitor

Phase I

N H

Cl

S N

O

CC(NC1=CC=C([C@H](C)C(NC2=NC =C(C(C)C)S2)=O)C=C1)=O 492445-28-0

Cl NH

O

O NH

NCGC00263091

AT-7519

CDK1/2 Inhibitor

N S

O

O NH

S NH

NCGC00263167

SNS-032

BMS-387032

CDK2,7,9 Inhibitor

N

Phase II N

N HN

N

PHA-793887

CDK1,2,3,4,5 Inhibitor

Phase I

O=C(C1CCNCC1)NC2=NC=C(SCC3 =NC=C(C(C)(C)C)O3)S2 345627-80-7

H N

O

NCGC00263168

ClC1=C(C(NC2=CNN=C2C(NC3CCN CC3)=O)=O)C(Cl)=CC=C1 902135-89-1

N H

HN N

Phase II

186692-46-6

O

CC1(C)N(C(C2CCN(C)CC2)=O)CC3= C1NN=C3NC(CC(C)C)=O 718630-59-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES HCl

HN N

N N H

N

NCGC00263129

PD-0332991

CDK4, 6 Inhibitor

CAS #

O

N

N

O

CC(C1=CN=C(NC2=CC=C(N3CCNC C3)C=N2)N=C1N4C5CCCC5)=C(C(C )=O)C4=O.Cl 571190-30-2

Phase II O Cl

O N

NCGC00092289

DA-3003-1

NSC-663284

Cell Division Cycle CDC25 Phosphatase Inhibitor

N H

N

O=C(C(Cl)=C1NCCN2CCOCC2)C3= C(N=CC=C3)C1=O 383907-43-5

O

Preclinical

O O S NH 2 F H2N

N

N

NCGC00263151

JNJ-7706621

Aurora Kinase Inhibitor

CDK1/Cyclin B/CDK2/Cyclin A Inhibitor

Preclinical

O=C(N1N=C(NC2=CC=C(S(N)(=O)= O)C=C2)N=C1N)C3=C(F)C=CC=C3F 443797-96-4 H N

S

H N

S

NH

N

O

F

N N

N

NCGC00242482

SNS-314

Aurora-A/B/C Kinase Inhibitor

O OH S O

Preclinical

H N Cl

O

O=C(NC1=NC=C(CCNC2=NC=NC3= C2SC=C3)S1)NC4=CC(Cl)=CC=C4.O S(C)(=O)=O 1146618-41-8

HN N HN

H N

N

NCGC00168110

Tozasertib

MK-0457, VX680

N

N

O=C(C1CC1)NC(C=C2)=CC=C2SC3 =NC(N4CCN(C)CC4)=CC(NC5=CC(C )=NN5)=N3 639089-54-6

O

S

N


Bcr-Abl, Flt3, Jak2 Inhibitor

Discontinued Cl F

H N

N N OMe

NCGC00263271

Alisertib

MLN-8237

Aurora-A inhibitor

O

N

OMe OH

phase II

OC(C(C=C1)=C(OC)C=C1NC2=NC3= C(C=N2)CN=C(C4=C(F)C=CC=C4OC )C5=CC(Cl)=CC=C53)=O 1028486-01-2

N H N

O N

N N

OMe

O=C([C@H](OC)C1=CC=CC=C1)N(C 2)CC3=C2C(NC(C4=CC=C(N5CCN(C )CC5)C=C4)=O)=NN3 827318-97-8

HN O

NCGC00263203

Danusertib

PHA-739358


FGFR1/RET/TRKA Inhibitor

Phase II N

H N

N

NH2

S

N

N

CC1=C(SC(N)=N1)C2=NC(NC3=CC= C(N4CCOCC4)C=C3)=NC=C2 693228-63-6

O

NCGC00263204

CYC-116


VEGFR-2 Inhibitor

Phase II N

N

N O

HO

NH O NH

F

NCGC00263089

AZD-1152-HQPA

Aurora-A/B Inhibitor

Phase II

N

N H

N

H2N N

S O N

NCGC00263094

AMG-900


Phase I

FC1=CC=CC(NC(CC2=NNC(NC3=N C=NC4=C3C=CC(OCCCN(CCCO)CC )=C4)=C2)=O)=C1 722544-51-6

N H

N

N

CC1=CSC(C(C2=C3C=CC=C2)=NN= C3NC(C=C4)=CC=C4OC5=C(C6=CC =NC(N)=N6)C=CC=N5)=C1 945595-80-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

N N

N

N NH

CN(CC1)CCN1C2=NC(/C=C/C3=CC= CC=C3)=NC(NC4=NNC(C)=C4)=C2 934353-76-1

HN N

NCGC00263178

ENMD-981693

ENMD-2076

Aurora-A Inhibitor

Flt3/VEGFR-2 Inhibitor

Phase II NH F3C

O

N

N NH

N

NCGC00250407

CHIR-265

RAF-265

Raf kinase B/C inhibitor

N

CF3

Phase II H N

N

O

H N

N

O

NCGC00250380

AZ-628

Raf kinase B/C Inhibitor

CN(C(NC1=CC=C(C(F)(F)F)C=C1)=N 2)C(C2=C3)=CC=C3OC4=CC(C5=NC (C(F)(F)F)=CN5)=NC=C4 927880-90-8

CC(C#N)(C)C1=CC=CC(C(NC2=CC= C(C)C(NC3=CC=C(N=CN(C)C4=O)C 4=C3)=C2)=O)=C1 878739-06-1

N

Preclinical F O

Cl

NCGC00250399

Vemurafenib

PLX-4032, Zelboraf, RO5185426

O O N S H

F

Raf kinase B Inhibitor

O=C(C1=C(F)C(NS(CCC)(=O)=O)=C C=C1F)C2=CNC3=NC=C(C4=CC=C( Cl)C=C4)C=C32 918504-65-1

N H

N

Approved F O

O O N S H

Cl F N H

N

NCGC00187911

PLX-4720


ClC1=CN=C(NC=C2C(C3=C(F)C(NS( CCC)(=O)=O)=CC=C3F)=O)C2=C1 918505-84-7

Preclinical HO N

NCGC00263179

AR-00341677

GDC-0879


OH

N N

OCCN1N=C(C2=CC=NC=C2)C(C3=C C=C(/C(CC4)=N/O)C4=C3)=C1 905281-76-7

N

Preclinical

F

NCGC00188380

RDEA-119

O O S NH HN O

HO

BAY-86-9766, AR119 Mek 1/2 inhibitor

Selumetinib

ARRY-142886, AZD-6244

I F

HO

Phase II HO

NCGC00189073

F

O

H N

O

Cl

H N F

N

Br

N

Mek1/2 inibitor

Erk inibitor

O=S(C1(C[C@H](O)CO)CC1)(NC2=C (OC)C=C(F)C(F)=C2NC3=CC=C(I)C= C3F)=O 923032-37-5

phase II

CN1C2=CC(C(NOCCO)=O)=C(NC3= CC=C(Br)C=C3Cl)C(F)=C2N=C1 606143-52-6

F H N

F NH I

NCGC00189075

PD-0325901

PD-325901

MEK inhibitor

O

O

OH OH

F

Phase I F O

NCGC00263180

Trametinib

GSK1120212B/JTP74057

I

HN

N O

N N

O O

Mek 1/2 inhibitor

Phase III

OC[C@H](CONC(C1=C(C(F)=C(C=C 1)F)NC2=C(C=C(C=C2)I)F)=O)O 391210-10-9

N H

O=C(N(C1CC1)C(N(C2=CC=CC(NC( C)=O)=C2)C3=C4C)=O)C3=C(NC5=C C=C(I)C=C5F)N(C)C4=O 871700-17-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

HO

NCGC00263187

TAK-733

MEK inhibitor

O

HN

N

N

F

N OH

O=C1C2=C(N(C)C(C(F)=C2NC3=CC =C(I)C=C3F)=O)N=CN1C[C@@H](O) CO 1035555-63-5

O

Phase I EtO

H N

N N

N N

O

N

CN(C1=CN=C(NC2=C(OCC)C=C(N3 CCC(O)CC3)C=C2)N=C1N(C)C4=C5 C=CC=C4)C5=O 1234480-50-2

HO

NCGC00250385

XMD8-92

ERK5/BMK1 inhibitor

preclinical NH

Cl N

H N

N F

NCGC00242487

NCGC00242487

ERK inhibitor

NH

Cl

O OH

Preclinical O

N

NCGC00263196

S6K-18

S

O

N H

p70 ribosomal S6 kinase (S6K1) inhibitor

O=C(NC1=C(C(O)=O)C=C(C(C)(C)C) S1)NC2=CC(C=NN3)=C3C=C2 1265789-88-5

Preclinical N

N HN

N

NCGC00263134

N

p70 ribosomal S6 kinase (S6K1) inhibitor

PF-4708671

NCGC00263133

PF-573228

PF-562271

CCC1=C(N2CCN(CC3=NC4=C(C=C C(C(F)(F)F)=C4)N3)CC2)N=CN=C1

Preclinical O

H N

PF-431396

CF3

N

N H

Focal Adhesion Kinase (FAK) Inhibitor

CF3

N

O

NCGC00242495

N H

N

O

O OH S O

S

N

N

Discontinued H N

S O O

Focal Adhesion Kinase (FAK) Inhibitor

N

F3C

Preclinical

H N

N

N H

O

O

N

Phase II H N

N H

O N

S N

N N H

NCGC00188382

NCGC00188382

ITK inhibitor

IRAK1,4 inhibitor

OH

Preclinical NH

OMe

N S

N

S O

NCGC00229512

ITK inhibitor

Preclinical

OC(C)(C)CN1C2=CC=C(CN[C@@H]( C)C(C)(C)C)C=C2N/C1=N\C(C3=CC= C(C4=CNN=C4)S3)=O 1149753-56-9

O

O HN

NCGC00229512

CS(C1=CC=CC(CNC2=C(C(F)(F)F)C =NC(NC3=CC=C(NC(CC4)=O)C4=C3 )=N2)=C1)(=O)=O 869288-64-2

NC1=NC=NC2=C1C(C(C=C3)=CC=C 3OC4=CC=CC=C4)=NN2[C@@H]5C CCN(C(C=C)=O)C5 936563-96-1

N

N

Btk/Lck/Lyn inhibitor

O=S(C1=CC=C(C)C=C1)(O)=O.CN(S (C)(=O)=O)C2=NC=CC=C2CNC3=NC (NC4=CC=C(NC(C5)=O)C5=C4)=NC =C3C(F)(F)F 939791-38-5

O

H2N

PCI-32765

1255517-76-0

N

N

NCGC00187912

O=C(C1=CC(C2=NC(NC3=CC=C(F)C =C3Cl)=NC=C2C)=CN1)N[C@@H](C 4=CC=CC(Cl)=C4)CO 896720-20-0

OH

H N

H N

CAS #

I

F

N

CC1=C(SC2=CN=C(NC(C3=CC=C(C NC(C(C)(C)C)C)C=C3)=O)S2)C=C(C( N4CCN(C(C)=O)CC4)=O)C(OC)=C1 439575-02-7

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N O

CO[C@@H]1[C@H](N(C(c2ccccc2)= O)C)C[C@H]3O[C@]1(n(c4c5cccc4)c 6c5c(CNC7=O)c7c8c6n3c9c8cccc9)C .O 120685-11-2

O H2O

NCGC00241102

Midostaurin

CGP-41251/PKC412 PKC/flt3 inhibitor

N

N

O

Phase II

N H H N

O

O

N

N

O=C(N1)C(C2=CN(C)C3=C2C=CC=C 3)=C(C4=CN(C5CCN(CC6=CC=CC= N6)CC5)C7=C4C=CC=C7)C1=O 170364-57-5

N N

NCGC00238452

Enzastaurin

LY-317615

PKCa, PKCb, PKCg inhbitor

Phase III H N

O

N

N H

NCGC00263095

Sotrastaurin

AEB-071

PKC inhibitor

Ruboxistaurin mesilate

Phase II

H N

O

N O O S OH O

LY-333531

PKC beta Inhibitor

O=C(N1)C(C2=NC(N3CCN(C)CC3)= NC4=CC=CC=C42)C(C5=CNC6=CC= CC=C56)C1=O 425637-18-9

N N N

O

NCGC00263119

O

O=C(N1)C(C2=CN3C4=C2C=CC=C4) C(C5=CN(CCO[C@H](CN(C)C)CC3) C6=C5C=CC=C6)C1=O.CS(O)(=O)= O 192050-59-2

N

N

Phase III N NH

N N

N

HN

NCGC00263018

NCGC00263018

Brk/PTK6 inhibitor

Brk/PTK6 inhibitor

Preclinical

CC(N=C1NC2=C(F)C=C(C(N3CCNC C3)=O)C=C2)=CN4C1=NC=C4C5=C NN=C5 1338249-84-5

NH N

F O

O

N S

N

NH2 MeO

NCGC00242217

Polo-like Kinase-1 (Plk-1) Inhibitor

GW 843682X

PKK3 inhibitor

O N H

NCGC00253438

BI-2536

NC(C1=C(OCC2=CC=CC=C2C(F)(F) F)C=C(N3C=NC4=C3C=C(OC)C(OC) =C4)S1)=O 660868-91-7

Preclinical N


CF3

O MeO

N

N

OMe

N H

O

CN(C1=CN=C(NC2=CC=C(C(NC3CC N(C)CC3)=O)C=C2OC)N=C1N(C4CC CC4)[C@@H]5CC)C5=O 755038-02-9

N

N

Phase II N N

O

NCGC00263087

Volasertib

BI-6727


OMe

N H

N

S NH2 O

GSK-461364A

Phase I

N

NCGC00250376

KN-93

CF3

N N

HO O

Calmodulin-Dependent Protein Kinase II Inhibitors

N

Cl

Preclinical

CN(C1=CN=C(NC2=CC=C(C(N[C@ @H]3CC[C@@H](N4CCN(CC5CC5) CC4)CC3)=O)C=C2OC)N=C1N(C(C) C)[C@@H]6CC)C6=O 755038-65-4

O N

NCGC00263112

O

Phase II N


N

N

N H

CN(CC1)CCN1CC2=CC(N(C3=CC(O[ C@H](C)C4=CC=CC=C4C(F)(F)F)=C (C(N)=O)S3)C=N5)=C5C=C2 929095-18-1

O O S

N

OMe

OCCN(S(C1=CC=C(OC)C=C1)(=O)= O)C2=CC=CC=C2CN(C)C(/C=C/C3= CC=C(Cl)C=C3)=O 139298-40-1

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N S O O

N

N N

CN(S(C1=CC=CC2=C1C=CN=C2)(= O)=O)[C@@H](CC3=CC=C(OS(C4= CC=CC5=C4C=CN=C5)(=O)=O)C=C 3)C(N6CCN(C7=CC=CC=C7)CC6)=O 127191-97-3

O O S O

NCGC00162398

Calmodulin-Dependent Protein Kinase II Inhibitors

KN-62

P2X7 Receptor Antagonist

N

Preclinical

H2N

N H

O N

NCGC00241982

GSK-269962A

ROCK 1, ROCK 2 Inhibitor

Preclinical

ROCK 1, ROCK 2 Inhibitor

Calcium Sensitizer/Leucine-Rich Repeat Kinase 2 (LRRK2; Dardarin) Inhibitor/ Preclinical

N

N

O

O

HCl

NCGC00092276

Y-27632

H N N

H

GSK-650394

SGK1 and SGK2 inhibitor

Preclinical

AZD-1480

Jak1/2 inhibitor

Phase II

Cl N

NH N NH

N

N

O

CP-690550

Jak inhibitor

phase III N

NCGC00244253

Ruxolitinib

Jak1/2 inhibitor

N H

CN([C@H]1CN(C(CC#N)=O)CC[C@ H]1C)C2=C3C=CNC3=NC=N2

477600-75-2

N

HN

Jakafi, INCB18424

935666-88-9

N

N

Tofacitinib

ClC1=C(NC2=NNC(C)=C2)N=C(N[C @@H](C)C3=NC=C(F)C=N3)N=C1

N

N

NCGC00229511

331752-47-7

O=C(O)C(C=C1)=C(C2CCCC2)C=C1 C3=CNC4=NC=C(C5=CC=CC=C5)C= C43 890842-28-1

N

NCGC00242486

O=C([C@H]1CC[C@@]([C@@H](C) N)([H])CC1)NC2=CC=NC=C2.Cl.Cl

OH

N HN

F

2

N H

N

O=C(NC1=CC(OC2=CC(N(CC)C(C3= NON=C3N)=N4)=C4C=N2)=CC=C1)C 5=CC=C(OCCN6CCOCC6)C=C5 850664-21-0

NH

HCl

O O

NCGC00242475

N N O

N

O

N N

N

N#CC[C@H]([C@H]1CCCC1)N2N=C C(C3=C4C(NC=C4)=NC=N3)=C2 941678-49-5

Approved O N

N H

H N

N N

NCGC00244257

CYT387

Jak1/2 inhibitor

N O

Phase II

N#CCNC(C1=CC=C(C2=CC=NC(NC 3=CC=C(N4CCOCC4)C=C3)=N2)C= C1)=O 1056634-68-4

HN O N N

NCGC00244256

Lestaurtinib

CEP-701, KT5555, SPM-924

Jak/Tyk/Flt inhibitor

O

OH

HO

Phase II

O=C1NCC2=C3C(N4C5=C3C=CC=C 5)=C6C(C(C=CC=C7)=C7N6[C@@H] 8C[C@](CO)(O)[C@]4(C)O8)=C21 111358-88-4

O O O

N N

NCGC00249346

SB1518

Jak2 inhibitor

Phase II

N H

N

C12=NC=CC(C3=CC(OCC/C=C/COC C4=C(OCCN5CCCC5)C=CC(N2)=C4 )=CC=C3)=N1 937272-93-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

F3C

NCGC00015610

Leflunomide

HWA-486/RS34821

Jak inhibitor

Dihydroorotate dehydrogenase (DHODH) inhibitor; PDGFR inhibitor/STAT6 inhibitor

CAS #

O N H

O N

Approved

O=C(C1=C(C)ON=C1)NC2=CC=C(C( F)(F)F)C=C2 75706-12-6

N N

F

NH

N N

FC1=CC(C2=C(N=C(C3=CN(C4CCN CC4)N=C3)C=N5)C5=CC=C2)=CC(F) =C1CN6CCOCC6 1092499-93-8

F N O

NCGC00263202

NVP-BSK805

Jak2 inhibitor

Preclinical O N

Br

NCGC00263102

Degrasyn

WP-1130

Jak2 Inhibitor

Syk Inhibitor; USP9X inhibitor/STAT-3 Inhibitor

N H

O=C(N[C@H](C1=CC=CC=C1)CCC)/ C(C#N)=C/C2=NC(Br)=CC=C2 856243-80-6

N

Preclinical Cl H N

H N

NCGC00263200

RO495

Tyk 2 inhibitor

N

N

O

Cl

NH2 N

O=C(C1=C(Cl)C=CC=C1Cl)NC2=CC =NC(NC3=CC(C)=NC(N)=N3)=C2 1258296-60-4

Preclinical F O

F N

H2N

NCGC00244250

NCGC00244250

Tyk 2 inhibitor

N

N

N

NC1=NC(NC2=CC=C(N(C)C)C=C2)= NN1C(C3=C(F)C=CC=C3F)=O 1261496-45-0

N H

Preclinical HO

O O

N O

NCGC00263116

ICG-001

Wnt Signaling Inhibitor

Apoptosis Inducer

O=C1CCN(C(NCC2=CC=CC=C2)=O) [C@H](N1[C@H]3CC4=CC=C(O)C=C 4)CN(CC5=CC=CC6=C5C=CC=C6)C 3=O 847591-62-2

N N

Preclinical

N H

N

N O

CC1=CC(C2=CC=C(CC(NC3=CC=C( C4=CC=CN=C4)C=C3)=O)C=C2)=CC =N1 1243243-89-1

N H

NCGC00263085

Wnt-C59

Wnt signaling modulator

Preclinical N

NH

O

NCGC00242498

D-4476

Casein Kinase I (CK1) Inhibitor

Preclinical

NH2

N

O

O

NC(C(C=C1)=CC=C1C2=NC(C3=CC =C4C(OCCO4)=C3)=C(C5=NC=CC= C5)N2)=O 301836-43-1

NH

Cl N

N HO

NCGC00263192

Silmitasertib

CX-4945

Casein Kinase II (CK2) Inhibitor

OC(C1=CC2=C(C3=CN=CC=C3C(NC 4=CC=CC(Cl)=C4)=N2)C=C1)=O 1009820-21-6

O

Phase I

H N F3CO

NCGC00250382

NVP-LDE-225

Erismodegib, LDE225 Smo Receptor Antagonist

O

N

N O

phase II

CC1=C(C(NC2=CN=C(N3C[C@H](C) O[C@H](C)C3)C=C2)=O)C=CC=C1C 4=CC=C(OC(F)(F)F)C=C4 956697-53-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

HN H H

O H H

H

NCGC00163474

Cyclopamine

Smo Receptor Antagonist

Preclinical

HO

[H][C@]1([C@H]2C)[C@](C[C@H](C) CN1)([H])O[C@@]32CC[C@@]4([H])[ C@]5([H])CC=C6C[C@@H](O)CC[C @]6(C)[C@@]5([H])CC4=C3C 4449-51-8

F N N

NCGC00263170

N

Smoothened (Smo) Receptor Antagonist

LY-2940680

N

N

O

CF3

CN(C(C1=C(C(F)(F)F)C=C(F)C=C1)= O)C(CC2)CCN2C3=C(C=CC=C4)C4= C(C5=CC=NN5C)N=N3 258861-20-9

N

Phase I OEt OEt

N

NCGC00263210

N H

Smoothened (Smo) Receptor Antagonis

SANT-2

H N

OEt O

Cl

Preclinical

ClC1=C(C2=NC(C=CC=C3)=C3N2)C =C(NC(C4=CC(OCC)=C(OCC)C(OC C)=C4)=O)C=C1 329196-48-7

MeHN N

F

N S

NCGC00263084

Hh-Ag1.5

FC1=C2C(C(Cl)=C(C(C(CC3=CC(C4 =CC=NC=C4)=CC=C3)N5CCC(NC)C C5)=O)S2)=C(F)C=C1 612542-14-0

O

Smoothened (Smo) receptor agonist

Cl

F

Preclinical

Cl

NCGC00242497

Vismodegib

GDC-0449/CUR691/RG-3616

Hedgehog antagonist

Cl

O

N

N H S O O

Approved

ClC1=CC=C(NC(C2=CC=C(S(C)(=O) =O)C=C2Cl)=O)C=C1C3=NC=CC=C3 879085-55-9

O NH F

O O

H N

F

NH

NCGC00263162

RO-4929097

R-4733/RG-4733

g-Secretase Inhibitor

Notch Receptor inhibitor

CF3

O=C1[C@@H](NC(C(C)(C)C(NCC(F) (F)C(F)(F)F)=O)=O)C2=C(C=CC=C2) C3=CC=CC=C3N1 847925-91-1

Phase II OH O Cl F F

NCGC00263184

MK-0752


FC1=CC=C(F)C([C@]2([S@@](C3=C C=C(Cl)C=C3)(=O)=O)CC[C@@H](C CC(O)=O)CC2)=C1 471905-41-6

S O O

Phase II O

O

H N

F

N

N H

O

O=C(N[C@@H](C)C(N[C@H]1C(C=C C=C2)=C2C(C=CC=C3)=C3N(C)C1= O)=O)CC4=CC(F)=CC(F)=C4 209984-56-5

F

NCGC00263188

NCGC00167803

YO-01027

GSI-9


AN37124/DAPT/LY374973

Preclinical O

H N

F

N H

O

O O

F


Preclinical

FC1=CC(F)=CC(CC(N[C@H](C(N[C @H](C(OC(C)(C)C)=O)C2=CC=CC= C2)=O)C)=O)=C1

208255-80-5

OH N

S N

F3C

NCGC00250397

NVP-XAV-939

XAV-939

TNKS1/TNKS2 Inhibitor

Preclinical

OC1=NC(C2=CC=C(C(F)(F)F)C=C2) =NC3=C1CSCC3 284028-89-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

Cl N

O

NCGC00263015

NCGC00263015

TLR4 (LPS) inhibitor

ClC1=CC=C(OCC(CN(CC2=C(C)N(C C3=C(C)C=CC=C3)N=C2C)C)O)C=C 1

N N

OH

Preclinical O N

HN MeO

N

CN(CC1)CCN1C(C=C2)=CC=C2C3= NC4=CC(OC)=C(OC)C=C4C(NCCN5 CCOCC5)=N3 1093135-60-4

N

MeO

N N

NCGC00263017

CPG-52364

TLR 7, 8 and 9 antagonist

Preclinical O N

NO2

N H

N

O=C(C1=CC=CC([N+]([O])=O)=C1)NC2=NC3=C(N2CCN4CCO CC4)C=CC=C3 509093-47-4

N

NCGC00186035

NCGC00186035

IRAK Inhibitor

O

Preclinical

N N

Cl

N NH

NCGC00241410

NCGC00241410

IRAK Inhibitor

O

O

N

O

NCGC00241411

NCGC00241411

IRAK Inhibitor

ClC1=CN2C(C=C1)=NC=C2C3=CC= CC(NC4CNC4)=N3 1044733-37-0

N H

Preclinical

NO2

N H

N

O=C(C(C)(C)C)OC1=CC2=C(N(CCC O)C(NC(C3=CC=CC([N+]([O])=O)=C3)=O)=N2)C=C1 509093-60-1

OH

Preclinical HO N

O

N N N

S

O

OC1=NN=C(SC2=NC=C([N+]([O])=O)S2)N1C3=CC(OCCO4)=C4C=C 3 883065-90-5

S NO2

NCGC00263145

BI-78D3

SAPK1 (JNK) Inhibitor

Preclinical N

N

NCGC00263146

SR-3306

JNK 1/2/3 Inhibitor

N

N

O

N

N

N H

N

Preclinical

CC(C=C1)=NC=C1C(N=C2)=NN2C(C =C3)=CC=C3NC4=NC=CC(C5=CC(N 6CCOCC6)=CC=C5)=N4 1128096-91-2

HO

NCGC00263141

STF-083010

Serine/Threonine Kinase/Endoribonuclease IRE1 Inhibitor

S

N S O O

O=S(C1=CC=CS1)(/N=C/C2=C(C=CC =C3)C3=CC=C2O)=O 307543-71-1

Preclinical H2N NH

N

CF3

S S

O

NCGC00250383

Irestatin 9389

IRE1alpha/XBP-1 inhibitor

NC1=C(C(NC2=NC(C)=CS2)=O)SC3 =C1C(C(F)(F)F)=C4C(CCC4)=N3 626221-47-4

N

Preclinical

Br

O

H N

N N NH

NH N

NCGC00242491

SB-265610

CXCR2 Antagonist

Preclinical

O=C(NC1=C2N=NNC2=C(C#N)C=C1 )NC3=CC=CC=C3Br 211096-49-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES H N

N

O

N

N

N

CC1=CC=CC(/C=N/NC2=NC(OCCC3 =CC=CC=N3)=NC(N4CCOCC4)=C2) =C1 541550-19-0

N O

NCGC00263093

Apilimod

STA-5326

IL-12 Production Inhibitor

CAS #

Phase II S

NCGC00263128

CXCR1/CXCR2 Receptor Antagonist

PD-0220245

Cl

N

Cl

N

S

N

Preclinical S

O

HCl OH NH2 OH

Cl

NCGC00250388

KRP 203

KNF-299

S1P1/3/4 agonist

Phase II H N

O

N

AMG-47a

Lck inhibitor

N H

Preclinical

CC(C=CC(C(NC1=CC=CC(C(F)(F)F) =C1)=O)=C2)=C2C3=CC4=CN=C(NC CN5CCOCC5)N=C4C=C3 882663-88-9

N

Cl

N H2N

N

N

NCGC00242499

Pim 1 inhibitor 2

Pim-1 inhibitor

ClC1=C(CCC(N)(CO)CO)C=CC(SC2= CC(OCC3=CC=CC=C3)=CC=C2)=C1 .Cl 509088-69-1

CF3

N

O

NCGC00263206

ClC1=C(Cl)C=C(N=C(NCCCCN(CC)C C)C(C2=CC=C(C3=CC=CS3)S2)=N4) C4=C1 239094-97-4

NH

NC1=NC=CC(C2=CC3=C(C4=CC=C( Cl)C=C4)ON=C3C=C2)=N1 477845-12-8

O

Preclinical N N H

N

N

N

OCF3

NCGC00263186

SGI-1776

SG-0407

Pim-1/Flt3 Inhibitor

Discontinued OMe

H N

N

H N

S

O

O

O=C(NC(C1=NC=CS1)C)NC(C(OC)= C2)=CC=C2OC3=CC=NC4=CC(OC)= C(OC)C=C43 623142-96-1

MeO MeO

NCGC00263193

KI-20227

CSF1R (c-FMS) Inhibitor

N

Preclinical Br

HCl

HCl

H2N

N N

N

NCGC00092381

ABT-702

Adenosine Kinase Inhibitor

OMe N

NCGC00263090

AZ-3146

monopolar spindle 1 (Mps1) kinase inhibitor

O

N N

Preclinical

H N

N

N N

Preclinical O N

N N H

N N

N N OH

MK-1775

Wee1 Kinase Inhibitor

Phase II

NC1=C2C(N=C(C=C2C3=CC(Br)=CC =C3)C4=CN=C(C=C4)N5CCOCC5)= NC=N1.Cl.Cl 214697-26-4

O=C1N(C)C2=CN=C(NC3=C(OC)C= C(OC4CCN(C)CC4)C=C3)N=C2N1C 5CCCC5 1124329-14-1

O

N

O

N

NCGC00263183

CN(CC1)CCC1CNC(C=C2)=NN3C2= NC=C3C4=CC=CC(OC(F)(F)F)=C4 1025065-69-3

O=C1N(CC=C)N(C2=CC=CC(C(C)(O )C)=N2)C3=NC(NC4=CC=C(N5CCN( C)CC5)C=C4)=NC=C31 955365-80-7

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES F

CAS #

F N

N N O

NCGC00263197

BMS-5

LIMK1/LIMK2 inhibitor

N

AMG-Tie2-1

Tie-2 inhibitor

NH

FC(F)C1=NN(C2=C(Cl)C=CC=C2Cl)C (C3=CN=C(NC(C(C)C)=O)S3)=C1 1338247-35-0

Preclinical H N

O

N H

NCGC00263199

CC1=CC=C(C(NC2=CC=CC(C(F)(F)F )=C2)=O)C=C1OC3=NC=CC=C3C4= CC=NC(NC)=N4 870223-96-4

Preclinical N NH S

N H

NVP231

Ceramide kinase inhibitor

CF3

O

N

N

O

NCGC00263217

Cl

S Cl

Ph O

Preclinical

O=C(NC1=CC(SC(NC(C2=CC=CC=C 2)=O)=N3)=C3C=C1)C4C5CC(C6)CC 4CC6C5 362003-83-6

OH OH

O[C@@H]([C@@H](CO)NC(CCCCC CCCCCCCC)=O)C1=CC=C([N+]([O])=O)C=C1 35922-06-6

HN

O2N

O

NCGC00263224

D-NMAPPD

ceramidase inhibitor

Preclinical H N

NCGC00188865

Pazopanib

GSK786034/Votrient/Ar mala multi-kinase

N

N

N N

N

CN(C1=NC(NC2=CC=C(C)C(S(N)(=O )=O)=C2)=NC=C1)C3=CC4=NN(C)C( C)=C4C=C3 635702-64-6

O S NH2 O

Approved

O N H

NH

S O

O

N

NCGC00244252

TG-101348

multi-kinase

Phase II H N

N

NCGC00242478

Alvespimycin hydrochloride

17-DMAG/BMS826476/NSC707545

O HCl

O

O

Heat Shock Protein 90 (hsp90) Inhibitor

N

N H

N

N H O O

O HO

O

NH2

Discontinued

O=S(C1=CC=CC(NC2=NC(NC3=CC= C(OCCN4CCCC4)C=C3)=NC=C2C)= C1)(NC(C)(C)C)=O 936091-26-8 O=C(C(NCCN(C)C)=C1C[C@@H](C) C[C@H](OC)[C@H](O)[C@@H](C)/C =C(C)/[C@H](OC(N)=O)[C@@H](OC )\C=C/C=C(C)/C2=O)C=C(N2)C1=O. Cl 467214-21-7

O O

HO

NCGC00161410


CCT-018159

HO

Preclinical

CC1=C(C2=CC(OCCO3)=C3C=C2)C( C4=CC(CC)=C(O)C=C4O)=NN1 171009-07-7

N N H

Cl N

N H2N

NCGC00247877

CNF-2024

BIIB-021


N

OMe

N

ClC1=C2C(N(CC3=NC=C(C)C(OC)= C3C)C=N2)=NC(N)=N1

N

Phase II

N

HO

NCGC00247878

NVP-AUY922

AUY-922/VER52296


HN

Phase II

OH

O N

O

848695-25-0

O

OC1=CC(O)=C(C2=C(C3=CC=C(CN4 CCOCC4)C=C3)C(C(NCC)=O)=NO2) C=C1C(C)C 747412-49-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES O N

NCGC00183656

Elesclomol

STA-4783

Heat Shock Protein 70 (hsp70) Inducer

S

CAS #

O

N H

N

N H

S=C(N(NC(CC(NN(C)C(C1=CC=CC= C1)=S)=O)=O)C)C2=CC=CC=C2 488832-69-5

S

Phase III NH2 N

N

N O

NCGC00263143


VER-155008

N H

N

N

HO

Preclinical

O[C@H]1[C@@H](O)[C@H](N2C(NC C3=CC(Cl)=C(Cl)C=C3)=NC4=C2N= CN=C4N)O[C@@H]1COCC5=CC=C( C#N)C=C5 1134156-31-2

Cl

O

Cl OH

O HN O O N

NCGC00250390

Histone Deacetylase (HDAC) 6 Inhibitor

ISOX

Preclinical

O

NCGC00168085

Vorinostat

HO

Approved

H N

O

O

Zolinza, MK-0683, Histone Deacetylase (HDAC) SAHA 1/2/3/6 Inhibitor

O=C(C1=NOC(C2=CC=C(NC(OC(C)( C)C)=O)C=C2)=C1)NCCCCCCC(NO) =O 1045792-66-2

OH

HN N H

O

N H

ONC(CCCCCCC(NC1=CC=CC=C1)= O)=O 149647-78-9 O N H

O

NCGC00263153

Histone Deacetylase (HDAC) 1/2 Inhibitor

AR-42

O=C(NC1=CC=C(C(NO)=O)C=C1)[C @@H]([C@H](C)C)C2=CC=CC=C2 935881-37-1

Phase II O

O O S

NCGC00263155


Belinostat

OH

N H

N H

N H

OH

Phase II

O=S(NC1=CC=CC=C1)(C2=CC=CC(/ C=C/C(NO)=O)=C2)=O 414864-00-9

O N

NCGC00263182

Mocetinostat

MG-0103/MGCD- Histone Deacetylase (HDAC) 1 0103 Inhibitor

N H

H N

N

Phase II N H

NCGC00263117

Panobinostat

LBH-589/NVPLBH-589

Histone Deacetylase (HDAC) Inhibitor

O=C(NC1=C(N)C=CC=C1)C(C=C2)= CC=C2CNC3=NC(C4=CC=CN=C4)= CC=N3 726169-73-9

NH2

N

H N

NH

OH

O

CC1=C(CCNCC2=CC=C(/C=C/C(NO) =O)C=C2)C3=CC=CC=C3N1 404950-80-7

N

O=C(NO)/C=C/C1=CC=C(N(CCN(CC )CC)C(CCCC)=N2)C2=C1 929016-96-6

Phase III O HO

N

N H

N

NCGC00263136

Pracinostat

SB-939


Phase II O

O

HN

NCGC00263220

Romidepsin

FK-228/NSC630176

Histone Deacetylase (HDAC) Inhibitor

O

NH

N H

O

S S

O

H N O

Approved

O=C1C[C@H](O2)/C=C/CCSSC[C@ H](C(N/C(C(N[C@H](C2=O)[C@H](C) C)=O)=C\C)=O)NC([C@@H]([C@H]( C)C)N1)=O 128517-07-7

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N

N H

N

N

NCGC00182052

SRT1720

O=C(NC1=C(C2=CN3C(SC=C3CN4C CNCC4)=N2)C=CC=C1)C5=NC6=CC =CC=C6N=C5 1001645-58-4

NH N

Histone Deacetylase/SIRT1 Activator

N

S

Preclinical Cl

NCGC00242458

EX-527

SEN-0014196

Histone Deacetylase SIRT1 Inhibitor

N H

O=C(N)C(CCC1)C2=C1C(C=C(Cl)C= C3)=C3N2 49843-98-3

NH2

O

Phase I O NH2

NCGC00165833

Entinostat

MS-27-275/MS275/NSC-706995

N H

H N

O N

NC1=C(NC(C2=CC=C(CNC(OCC3=C N=CC=C3)=O)C=C2)=O)C=CC=C1 209783-80-2

O

HDAC1 Inhibitor

Phase II OH O OH

NCGC00263121

Histone acetyltransferase inhibitor

MG-149

OC1=C(C(O)=O)C(CCC2=CC=C(CC CCCCC)C=C2)=CC=C1

Preclinical H N

N

NCGC00250404

Veliparib

ABT-888/NSC737664

N H

PARP-1/PARP-2 Inhibitor

1243583-85-8

NH2

O

O=C(N)C1=C2C(NC([C@@]3(C)CCC N3)=N2)=CC=C1 912444-00-9

Phase II O F

N N

NCGC00238451

Olaparib

AZD-2281/KU0059436

O=C1C2=CC=CC=C2C(CC3=CC(C(N 4CCN(C(C5CC5)=O)CC4)=O)=C(F)C =C3)=NN1 763113-22-0

O

N NH O


Phase II N O

N NH

N

NCGC00168108

AG-14361

TBI-361

PARP-1 Inhibitor

Preclinical

O=C1NCCN2C3=C(N=C2C4=CC=C( CN(C)C)C=C4)C=CC=C31 328543-09-5

N H

HN O

O OH P OH

NH

NCGC00263173

Rucaparib

AG-014699/PF01367338

HO F


Phase II

O=C1NCCC2=C(C3=CC=C(C=C3)CN C)NC4=C2C1=CC(F)=C4.OP(O)(O)= O 459868-92-9

O O2N

NH2

I

NCGC00263096

Iniparib

PARP-1 Inhibitor

Phase III Cl

O N H

NCGC00249611

Ixazomib

MLN-2238

Proteasome Inhibitor

Phase II

Cl

H N

IC1=C([N+]([O])=O)C=C(C(N)=O)C=C1

160003-66-7

ClC1=C(C(NCC(N[C@@H](CC(C)C) B(O)O)=O)=O)C=C(Cl)C=C1

1072833-77-2

OH B OH

O

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

NCGC00249613

Carfilzomib

ONO-7057, PR171


O

H N

N

Ph

O

NCGC00242506

Bortezomib


O

O

NCGC00263175

Tosedostat

Aminopeptidase N Inhibitor

N H

OH

NCGC00263218

Teriflunomide

MMP-2, 9 Inhibitor

O

ONC([C@@H](O)[C@@H](CC(C)C)C (N[C@@H](C1=CC=CC=C1)C(OC2C CCC2)=O)=O)=O 238750-77-1

O

Phase II

Dihydroorotate Dehydrogenase (DHODH) Inhibitor

CF3

O N H

CN

C/C(O)=C(C(NC1=CC=C(C(F)(F)F)C= C1)=O)\C#N 163451-81-8

Approved O O S

NCGC00263127

PD-166793

MMP-13 Inhibitor

MMP-2 (Gelatinase A) Inhibitor/MMP-3 (Stromelysin 1) Inhibitor

OH O

Preclinical

Br

O

MeO N S O

CC(C)C1=C2C(S(N(COC3=CC(N(C= CC=C4OCCN5CCCCC5)C4=N3)=O) C2=O)(=O)=O)=CC(OC)=C1 344930-95-6

N

O

N O

NCGC00167751

SSR-69071

Leukocyte Elastase Inhibitor

Discontinued O

BrC1=CC=C(C2=CC=C(S(C[C@@H]( [C@@H](C)C)C(O)=O)(=O)=O)C=C2) C=C1 199850-67-4

N

O O

O=C(N[C@H](C(N[C@H](B(O)O)CC( C)C)=O)CC1=CC=CC=C1)C2=NC=C N=C2 179324-69-7

O

H N

OH

A-771726/HMR1726

O

OH B OH

H N

N H

N

Caspase 3 Activator, NF-kappaB (NFKB) Activation Inhibitor Approved

HO

BB-76163/CHR2797

O N H

O

phase II

N

Velcade, LDP341, MLN-341

O

H N

N H

O

O

CAS #

O=C(CN1CCOCC1)N[C@@H](CCC2 =CC=CC=C2)C(N[C@@H](CC(C)C)C (N[C@@H](CC3=CC=CC=C3)C(N[C @@H](CC(C)C)C([C@@]4(OC4)C)= O)=O)=O)=O 868540-17-4

O OH

N

NH

O=C1N([C@@H](CC2=CNC3=C2C= CC=C3)C(O)=O)C(C4=CC=CC=C41) =O 48208-26-0

O

NCGC00014891

RG-108

NSC-401077

DNA Methyltransferase (DNMT) Inhibitor

Preclinical N HN MeO

NCGC00185850

BIX-01294

Histone-lysine Nmethyltransferase EHMT2 Inhibitor

N

MeO

CN(CCC1)CCN1C2=NC3=CC(OC)=C (OC)C=C3C(NC4CCN(CC5=CC=CC= C5)CC4)=N2 935693-62-2

N

N

N

Preclinical N N

N

S

CO2tBu N

NCGC00250412

JQ1

BRD4 inhibitor

Preclinical

ClC(C=C1)=CC=C1C2=N[C@@H](C C(OC(C)(C)C)=O)C3=NN=C(C)N3C4 =C2C(C)=C(C)S4 1268524-70-4

Cl

O NH S

HN

NCGC00185090

NCGC00185090

APE1 inhibitor

Preclinical

N S

O=C(C)NC1=C(C2=NC(C=CC=C3)=C 3S2)C(CNC4)=C4S1

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

OH N N

NCGC00241036

NCGC00241036

JMJ inhibitor

O

Preclinical

OC1=CC=C(C(O)=O)C2=CC(N3CCO CC3)=CN=C21

O

OH

OH N

H N

N

OC1=CC(C2=CC=C(C(NCCCN(C)C) =O)C=C2)=CC3=CC=CN=C31 1222800-79-4

O

NCGC00183808

NCGC00183808

JMJ inhibitor

Preclinical Cl N

N NH2

NCGC00250406

Tipifarnib

NSC702818/Zarnestra Farnesyltransferase Inhibitor

N

O

N[C@@](C1=CC=C(Cl)C=C1)(C2=C N=CN2C)C3=CC=C4N(C)C(C=C(C5= CC=CC(Cl)=C5)C4=C3)=O 192185-72-1

Cl

Phase III N COOH

NCGC00242489

LG100268

RXR agonist

CC(CCC1(C)C)(C)C2=C1C=C(C)C(C 3(CC3)C4=CC=C(C(O)=O)C=N4)=C2 153559-76-3

Preclinical O OH

NCGC00092284

AHPN

AGN-192837, AHPN, CD-437

O=C(C1=CC=C2C=C(C3=CC=C(O)C( C4(C5)CC6CC5CC(C6)C4)=C3)C=C C2=C1)O 125316-60-1

HO

RARgamma Agonist

Preclinical F

O OH

S N

O

NCGC00242477

AC-261066

RARbeta2 Agonist

O=C(O)C1=CC=C(C2=NC(OCCOCC CC)=C(C)S2)C=C1F 870773-76-5

O

Preclinical OH

O

NCGC00090752

Fenretinide

McN-R-1967, NSC374551, ST-602, SYT-101 RARbeta/gamma Agonist

CC1(C)C(/C=C/C(C)=C/C=C/C(C)=C/ C(NC2=CC=C(O)C=C2)=O)=C(C)CC C1 65646-68-6

N H

phase II O OH OH

HO

O=C(CO)[C@@]1(O)CC[C@@]2([H])[ C@]3([H])CCC4=CC(CC[C@]4(C)[C @@]3([H])[C@@H](O)C[C@@]21C)= O 50-23-7

H H

NCGC00022848

Hydrocortisone

immunosuppressant

Approved

H

O

OH OH

NCGC00242502

Dexamethasone

Decadron, DexaSite, Maxidex, ProDex, ISV-305, OTO-104 Antiinflammatory

HO F

Approved

O

H

O

O HO

N

NCGC00242504

Cortivazol

Approved

O OH

H

N

Glucocorticoid Receptor (GR) Agonist

H

H

O

O[C@]1(C(CO)=O)[C@H](C)C[C@@] 2([H])[C@]3([H])CCC4=CC(C=C[C@] 4(C)[C@]3(F)[C@@H](O)C[C@@]21 C)=O 50-02-2 CC1=C[C@]([C@@](C[C@@H](C)[C @]2(O)C(COC(C)=O)=O)([H])[C@]2( C)C[C@@H]3O)(C)[C@@]3([H])[C@] 4(C)C1=CC5=C(C=NN5C6=CC=CC= C6)C4 1110-40-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES HO

OH

CC1=C[C@]([C@@](C[C@@H](C)[C @]2(O)C(CO)=O)([H])[C@]2(C)C[C@ @H]3O)(C)[C@@]3([H])[C@]4(C)C1= CC5=C(C=NN5C6=CC=CC=C6)C4 4906-84-7

H

H

N N

NCGC00242505

Glucocorticoid Receptor (GR) Agonist

Deacetyl cortivazol

CAS #

OH

O

Preclinical N

NCGC00263148

Abiraterone

Androgen Biosynthesis Inhibitor

Cytochrome P450 CYP17 (17alpha-Hydroxylase/C17-20 Lyase) Inhibitor

H

C[C@]12C(C[C@@H](O)CC2)=CC[C @]3([H])[C@]1([H])CC[C@@]4(C)[C @@]3([H])CC=C4C5=CN=CC=C5 154229-19-3

H

H HO

Phase I OH H

MeO H

NCGC00094082

Hypoxia Inducible Factor 1-alpha Inhibitor

2-Methoxyestradiol

O[C@H]1CC[C@@]2([H])[C@]3([H])C CC4=CC(O)=C(OC)C=C4[C@@]3([H] )CC[C@@]21C 362-07-2

H

HO

Phase II OH OH HO

NCGC00015870

Quercetine

Sophoretin, Meletin

O

OC1=CC2=C(C(C(O)=C(C3=CC=C(O )C(O)=C3)O2)=O)C(O)=C1 117-39-5

OH

flavanoid

OH

Suppliment

O

H

[H][C@@]12CC[C@@]([C@@H](/C= C/[C@H](C)C(C)C)C)([H])[C@@]1(C) CCC/C2=C\C=C3C([C@H](C[C@@H] (C\3)O)O)=C 54573-75-0

H

NCGC00182058

Doxercalciferol

TSA-840

Vitamin D Analog

Approved

OH

HO

H

OH

C[C@H](/C=C/C=C/C(CC)(CC)O)[C@ @]1([H])CC[C@@]2([H])/C(CCCC21 C)=C/C=C3C[C@@H](O)C[C@H](O) C\3=C 134404-52-7

H

NCGC00242511

Seocalcitol

EB1089

Vitamin D Analog

OH

HO

Phase I

O

O

O=C(OC)C[C@@H]1[C@@H](C/C=C \CC)C(CC1)=O 39924-52-2

O

NCGC00242512

methyl jasmonate

cytochrome c release inducer

Preclinical OH O S O

O NH

NCGC00167977

Bicalutamide

ICI-176334, Casodex

N

F

Androgen Receptor Antagonist

Approved

Selective Androgen Receptor Modulators (SARM)

N OH H

O

O

NC-54


Phase III

CC(NC1=CC=C(OC[C@](C)(O)C(NC 2=CC(C(F)(F)F)=C([N+]([O])=O)C=C2)=O)C=C1)=O 401900-40-1

F S N

MDV-3100

CF3

Phase I N H

NCGC00263120

NO2

O

O

Andarine

O=C(NC1=CC=C(C#N)C(C(F)(F)F)=C 1)C(C)(O)CS(=O)(C2=CC=C(F)C=C2) =O 90357-06-5

F F

H N

NCGC00263150

F

N

N O

CF3

FC1=CC(N2C(C)(C)C(N(C3=CC(C(F) (F)F)=C(C#N)C=C3)C2=S)=O)=CC=C 1C(NC)=O 915087-33-1

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

N H

S N

RD-162

NC-53


O=C(NC)C1=CC=C(N2C3(CCC3)C(N (C4=CC(C(F)(F)F)=C(C#N)C=C4)C2= S)=O)C=C1F 915087-27-3

N

N CF3

O

NCGC00263137

CAS #

F

O

Preclinical S N N

N

Cl

O

Cl

NCGC00163107

Constitutive androstane receptor agonist

CITCO

ClC1=CC=C(C=C1Cl)CO/N=C/C2=C( C3=CC=C(Cl)C=C3)N=C4SC=CN42 338404-52-7

Cl

Preclinical

Cl

NCGC00015205

Constitutive Androstane Receptor Antagonist

PK-11195

Peripheral Benzodiazepine Receptor Antagonist/Pregnane X Receptor Agonist

N N

CCC(C)N(C)C(=O)c3cc1ccccc1c(n3)c2ccccc2Cl 85532-75-8

O

Preclinical

S

NCGC00163128

Pioglitazone HCl

AA-10090, U72107A, Actos, Glustin, Zactos

N

HCl

PPARgamma Agonists

O

CCC1=CN=C(CCOC2=CC=C(CC3C( NC(S3)=O)=O)C=C2)C=C1.Cl 112529-15-4

Approved N S HO

NCGC00092344

GW-0742

GW-610742

Insulin Sensitizer/PPARdelta Agonist

GSK-516, 501516 PPARdelta Agonist

F F

O=C(O)COC1=CC=C(SCC2=C(C)N= C(C3=CC=C(C(F)(F)F)C(F)=C3)S2)C =C1C 317318-84-6

F

O

Preclinical

OH

S S

F3C

GW-501516

F

S

O

N

NCGC00241455

O

NH

O

O

Phase II S O

NCGC00161599

Troglitazone

CI-991, CS-045, GR-92132X

CCL2 Expression Inhibitor

CC1=C(CSC2=CC=C(OCC(O)=O)C( C)=C2)SC(C3=CC=C(C(F)(F)F)C=C3) =N1 317318-70-0

O

EGR1 Expression Enhancer/Insulin Sensitizer/PPARgamma Agonist Discontinued

O

O

NH

O

CC1=C(C)C(O)=C(C)C2=C1OC(C)(C OC3=CC=C(CC4C(NC(S4)=O)=O)C= C3)CC2 97322-87-7

HO

N N

N N

O

NCGC00095150

Telmisartan

Angiotensin AT1 Antagonist

F3C

Cl N

NCGC00263111

GSK-3787

PPARdelta Antagonist

CN1C2=CC=CC=C2N=C1C3=CC(N( CC4=CC=C(C5=CC=CC=C5C(O)=O) C=C4)C(CCC)=N6)=C6C(C)=C3 144701-48-4

OH

PPARalpha Partial Agonist/PPARgamma Modulator Approved

S O O

H N

O=S(C1=NC=C(C(F)(F)F)C=C1)(CCN C(C2=CC=C(Cl)C=C2)=O)=O 188591-46-0

O

Preclinical O

F3C

NCGC00263123

MK-767

KRP-297

PPARalpha/gamma agonist

Discontinued

N H MeO

S O

NH

O

O=C(NCC1=CC=C(C(F)(F)F)C=C1)C 2=C(OC)C=CC(CC3C(NC(S3)=O)=O) =C2 213252-19-8

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES O

CAS #

O O O

O

HN

CC(OC1=CC=CC2=C1C=CN(CC(NC 3=CC=C(OCCO4)C4=C3)=O)C2=O)C (OCC)=O 868224-64-0

O N

NCGC00081778

SF1 (NR5A1) Receptor Antagonist

SID 7969543

O

Preclinical HO

N OH

NCGC00182055

Bazedoxifene

TSE-424/WAY140424

Selective Estrogen Receptor Modulators (SERM)

N

O

Approved

OC(C=C1)=CC2=C1N(C(C3=CC=C(O )C=C3)=C2C)CC4=CC=C(OCCN5CC CCCC5)C=C4 198481-32-2

O O O O

NCGC00163411

Inhibition of RNA polymerase II–mediated transcription

Triptolide

O

Preclinical HO

NCGC00263092

TNF-alpha-Converting Enzyme Inhibitor

Apratastat

O=C(OC1)C2=C1[C@@](C[C@H](O3 )[C@]43[C@@]56[C@@H](O6)[C@H ]7[C@@](O7)(C(C)C)[C@H]4O)([H])[ C@]5(C)CC2 38748-32-2

OH

H

Matrix Metalloproteinase Inhibitor

O S S N O O HN OH

O

Phase II

O=S(C1=CC=C(OCC#CCO)C=C1)(N 2[C@@H](C(NO)=O)C(C)(C)SCC2)= O 287405-51-0

O N N

CC1=C(C(NC2=CC=CC(C(F)(F)F)=C 2)=O)C=C(C3=CC=CC=C3)N1CCCN 4CCOCC4 883031-03-6

NH O

NCGC00263214

HC-067047

TRPV4 Antagonist

CF3

Preclinical O N H

N

NCGC00263016

DE-096

TRPV4 Antagonist

TNF-alpha Production Inhibitor

N

O=C(N(CCC1(CC2C3)CC3CC(C2)C1 )CCCCC)NCCCC4=CC=NC=C4 379262-36-9

Preclinical F OH

HCl

O

NCGC00161825

GSK-3965

GW-3965

ABCA1 Expression Enhancer

ABCA1 Expression Enhancer/Liver X Receptor (LXR) Agonist

F F

O

Cl N

O=C(CC1=CC=CC(OCCCN(CC(C2= CC=CC=C2)C3=CC=CC=C3)CC4=C C=CC(C(F)(F)F)=C4Cl)=C1)O.Cl 405911-17-3

Preclinical HCl

O HO

N

O

ClC1=C(C(F)(F)F)C=CC=C1CN(CC(C 2=CC=CC=C2)C3=CC=CC=C3)CCC OC4=CC=CC(CC(O)=O)=C4.Cl 405911-17-3

Cl

NCGC00161825

GSK-3965

GW-683965

ABCA1 Expression Enhancer

Liver X Receptor (LXR) Agonist

CF3

Preclinical

OMe N MeO N

NCGC00016925

Omeprazole

AGI-010/DM-3458 ABCC3 Expression Enhancer

H+/K+-ATPase Inhibitor

S O

N H

CC1=C(CS(C2=NC3=C(C=CC(OC)= C3)N2)=O)N=CC(C)=C1OC

Approved

73590-58-6

O OMe

OMe

NCGC00263219

Elacridar

P-Glycoprotein (MDR-1) Inhibitor

N

N H O

N H

Phase I OMe

OMe

O=C1C2=C(C(C(NC3=CC=C(CCN4C C(C=C(OC)C(OC)=C5)=C5CC4)C=C 3)=O)=CC=C2)NC6=C(OC)C=CC=C6 1 143664-11-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

OMe N N

O

N

O

O=C(NC(C=C1)=CC=C1N2C(C3=CC( OCO4)=C4C=C3)=NC(OC)=N2)CSC5 =CC=CC=C5 853625-60-2

S

HN O

NCGC00168109

Secin H3

GEF inhibitor

Preclinical

N O

Cl

NCGC00250389

CDIBA

Phospholipase C inhibitor

COOH

Preclinical O

HN

N

H H

O

H

MeO

NCGC00025091

U-73122

Phospholipase C Inhibitor

CC1=C(CCOC2=CC=C(C(O)=O)C=C 2)C3=CC(Cl)=CC=C3N1C(C4=CC=C C=C4)C5=CC=CC=C5 479422-22-5

Preclinical

C[C@@]12[C@](CC[C@@H]2NCCC CCCN3C(C=CC3=O)=O)([H])[C@]4([ H])CCC5=CC(OC)=CC=C5[C@@]4([ H])CC1 112648-68-7

OH

N

MeO

NCGC00263226

NCGC00161408

BAY-60-7550

anagrelide

Phosphodiesterase II (PDE2A) Inhibitor

Agrelin, Agrylin, Thromboreductin, Xagrid, BL-4162A, BMY-26538-01, KRN-654, SPDPhosphodiesterase III (PDE3) 422 inhibitor

N

MeO

O=C1NC(CC2=CC(OC)=C(OC)C=C2) =NN3C1C(C)N=C3[C@@H](CCC4=C C=CC=C4)[C@@H](C)O 439083-90-6

N

HN O

Preclinical

H N

N O

N

Cl

O=C1CN2CC3=C(Cl)C(Cl)=CC=C3N C2=N1.Cl 58579-51-4

HCl

Cl

Approved N

N

N

NCGC00162385

Olprinone

Loprinone

Phosphodiesterase III (PDE3) Inhibitor

N H

Phase II O

CC(NC(C(C#N)=C1)=O)=C1C(C=C2) =CN3C2=NC=C3 106730-54-5

O

MeO O

MeO N

NCGC00168459

Phosphodiesterase IIII (PDE4) inhibitor

NCGC00168459

COC1=CC(C2=NN=C3C=CC(C4=CC =C(OC)C(O[C@@H]5CCOC5)=C4)= NN32)=C(OC)C=C1 1172617-47-8

OMe N

N N

Preclinical OH

O N

NCGC00249759


NCGC00249759

CC(C)(O)CCC(C=C1)=CC=C1OCC2= CC3=CC=CN=C3C(C4=CC=CC(OC( F)F)=C4)=C2 1252807-76-3

OCHF2

Preclinical O OH

N

NCGC00250085


NVP-ABE171

Preclinical

N

O=C(O)C(C=C1)=CC=C1C2=CC3=C C=CN=C3C(C4=CC5=NON=C5C=C4 )=N2 426268-06-6

N N O

O H2N O O S O

NCGC00263118

Lirimilast

BAY-19-8004


Phase II

NH O O Cl Cl

NC(NC1=C(C(C2=C(Cl)C=C(Cl)C=C2 )=O)OC3=CC(OS(C)(=O)=O)=CC=C3 1)=O 329306-27-6

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES O

NCGC00159496

Sildenafil citrate

N

HN

O O S

Viagra, GHL-901, HIP-0908, NVDPhosphodiesterase V (PDE5) 401, UK-92480-10 inhibitor

OH

N

N

OH

O O

N

N

OH

OEt

HO

O

Approved

CAS #

O=S(C1=CC=C(OCC)C(C2=NC(C(CC C)=NN3C)=C3C(N2)=O)=C1)(N4CCN (C)CC4)=O.OC(C(CC(O)=O)(O)CC(O )=O)=O 171599-83-0

O

S

O N

O

NCGC00182037

Alacepril

N H

Angiotensin-I Converting Enzyme Cetapril, DU-1219 Inhibitor

Approved OH

NCGC00025323

Ubenimex

NK-421

Leukotriene A4 Hydrolase Inhibitor

O=C([C@H](C)CSC(C)=O)N1[C@H]( C(N[C@@H](CC2=CC=CC=C2)C(O) =O)=O)CCC1 74258-86-9

OH O

Membrane Alanine Aminopeptidase (Aminopeptidase N) Inhibitor

O

H N

OH

NH2 O

O=C(N[C@H](C(O)=O)CC(C)C)[C@ @H](O)[C@H](N)CC1=CC=CC=C1

approved

58970-76-6

O N

H2N

NH2

N

N

FC(C=CC=C1)=C1CN2C3=NC=CC= C3C(C4=NC(N)=C(N5CCOCC5)C(N) =N4)=N2 256498-66-5

N N

N

NCGC00263227

NCGC00016854

BAY-41-8543

Vinpocetine

Guanylate Cyclase Activator Calan, Cavinton, AY-27255, H-500, Org-30759, RGH4405 Na+ channel inhibitor

Preclinical

F

H N

N

CC[C@@]1([C@@]23[H])C=C(C(OC C)=O)N4C2=C(C5=C4C=CC=C5)CC N3CCC1 42971-09-5

O

PDE1 inhibitor

O

Approved NC MeO

NCGC00016083

Verapamil

E-0103

Calcium Channel Blocker

Dopamine D2 Antagonist/L-Type Calcium Channel Blocker Approved

OMe

N

OMe

MeO

CC(C)C(CCCN(C)CCC1=CC=C(OC) C(OC)=C1)(C#N)C2=CC(OC)=C(OC) C=C2 52-53-9

HCl H N MeO

NCGC00025015

O NO2

L-type Ca2+ channel blocker

(S )-(+)-Niguldipine

O=C(OC)C1=C(C)NC(C)=C(C(OCCC N2CCC(C3=CC=CC=C3)(C4=CC=CC =C4)CC2)=O)[C@H]1C5=CC=CC([N+ ]([O-])=O)=C5.Cl 113165-32-5

N

O O

Preclinical OMe

O S O

OMe

N

NCGC00025379

SR 33805

Ca

channel antagonist

CN1C2=CC=CC=C2C(C(C)C)=C1S(C 3=CC=C(OCCCN(C)CCC4=CC(OC)= C(OC)C=C4)C=C3)(=O)=O 121346-32-5

N

O

2+

Preclinical O

NH N

O N N

NCGC00159544

Zaldaride maleate

CGS-9343B/KW5617/Zy-17617B

Calmodulin Antagonist

CC1(CN2CCC(N3C(C=CC=C4)=C4N C3=O)CC2)C5=CC=CN5C6=CC=CC =C6CO1.O=C(/C=C\C(O)=O)O 109826-27-9

COOH COOH

Phase III

N

NCGC00015882

Riluzole

PK-26124/RP54274/Rilute

Glutamate Release Inhibitor

K(V)4.3 Channel Blocker/Sodium Channel Blockers

F3C Approved

NH2 O

S NC1=NC2=CC=C(OC(F)(F)F)C=C2S1 1744-22-5

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O=C(N[C@H]([C@H]1NCCCC1)C2= CC=CC=C2)C3=C(Cl)C(C(F)(F)F)=C C=C3.Cl

665571-23-8

HCl Cl

NCGC00247954

SSR-504734

GlyT-1 Inhibitor

NH

O

F3C

N H

Phase I HCl

MeO

O N

NCGC00263114

SCH-900435

Org-25935

GlyT-1 Inhibitor

OH

CN(CC(O)=O)C[C@H]1[C@@H](C2= CC=CC=C2)C3=CC=C(OC)C=C3CC1 .Cl 949588-40-3

Phase II

HN

HN O

O=C1C(C(NC2=C(C(C)(C)C)C=C(C( C)(C)C)C(O)=C2)=O)=CNC3=C1C=C C=C3 873054-44-5

OH

O

NCGC00242480

Ivacaftor

VX-770

CFTR Channel Activator

Approved OMe

MeO HCl

NCGC00181343

Ivabradine hydrochloride

O

Corlentor, Procoralan, S16257, S-16257-2 HCN [I(f)] Blockers

O=C(C1)N(CCCN(C)C[C@@H]2CC3 =C2C=C(OC)C(OC)=C3)CCC4=C1C= C(OC)C(OC)=C4.Cl 148849-67-6

MeO N

N

Approved

MeO

N

N

Cl-

N

CCN(C1=CC(NC)=[N+](C)C(C)=N1)C 2=CC=CC=C2.[Cl-] 133059-99-1

NH

NCGC00024929

ICI-D7288

ZD-7288

HCN [I(h)] Blockers

Phase II O

O N

N

Cl NH S O

HN HO S

NCGC00250409

GSK-1016790A

TRPV4 Agonist

Preclinical H N

N N

NCGC00092384

Fenobam

McN-3377

Cl

O

O

mgluR5 Antagonists

Phase II

H N

O=C(N[C@@H](CC(C)C)C(N1CCN(C ([C@H](CO)NS(C2=CC=C(Cl)C=C2Cl )(=O)=O)=O)CC1)=O)C3=CC4=CC=C C=C4S3 942206-85-1

Cl

O

ClC1=CC(NC(NC(N(C)C2)=NC2=O)= O)=CC=C1 57653-26-6

O

HCl N

NCGC00015682

MPEP

mgluR5 Antagonists

CC1=CC=CC(C#CC2=CC=CC=C2)= N1.Cl 96206-92-7

Preclinical N O

NH HCl O

NCGC00250378

Piboserod hydrochloride

N

SB-207266A

5-HT4 Antagonists

O=C(NCC1CCN(CCCC)CC1)C2=C3 N(CCCO3)C4=CC=CC=C42.Cl

Phase III

178273-87-5

O

HCl

N

N O

N O N

NCGC00015918

SB-224289

5-HT1B Agonist

5-HT1D Antagonist

Preclinical

O=C(C1=CC=C(C2=C(C)C=C(C3=NO C(C)=N3)C=C2)C=C1)N4C(C=C(C5( CCN(C)CC5)CO6)C6=C7)=C7CC4.Cl 180084-26-8

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

H N

O

HCl

N N

N

NCGC00015917

SB-206553

5-HT1A Receptor Partial Agonist 5-HT2B/C Antagonist

CN1C=CC2=C1C=C(CCN3C(NC4=C N=CC=C4)=O)C3=C2.Cl 158942-04-2

Preclinical O

H N

O=C(NC1(C(O)=O)C2CC3CC1CC(C2 )C3)C(C=C4C5=C(OC)C=CC=C5OC) =NN4C6=C7C(C=C(Cl)C=C7)=NC=C 6 146362-70-1

O

HOOC

N

N O

NCGC00242503

Meclinertant

SR-48692, Reminertant

Carboxypeptidase A Inhibitor

Neurotensin NTS1 Receptor Antagonist

N

Cl

Discontinued O

N

OMe

O H O S N

N

N

O=S(C1=CC=CN=C1C2=CC=C(C3=N N=CO3)C=C2)(NC4=NC=C(C)N=C4O C)=O 186497-07-4

N

NCGC00242479

Zibotentan

ZD-4054

Endothelin ETA Receptor Antagonist

N

Phase III O N

O Cl

Cl O

NCGC00167739

GW-4064X

GW-4064

Farnesoid X Receptor Agonist

Preclinical

Cl

OH

O

O=C(O)C1=CC=CC(/C=C/C2=CC=C( OCC3=C(C(C)C)ON=C3C4=C(Cl)C= CC=C4Cl)C=C2Cl)=C1 278779-30-9

F

N F

NCGC00263105

Turofexorate isopropyl

FXR-450/WAY362450/XL-335

N H

Farnesoid X Receptor Agonist

CC1(C)CN(C(C2=CC=C(F)C(F)=C2)= O)C=C(C(OC(C)C)=O)C3=C1C4=CC =CC=C4N3 629664-81-9

O O

Phase I O HO

NCGC00167811

Free Fatty Acid Receptor 1 Agonist

GW-9508

O

N H

O=C(CCC(C=C1)=CC=C1NCC2=CC( OC3=CC=CC=C3)=CC=C2)O 885101-89-3

Preclinical OEt OEt

N

O O

HN

NCGC00263225

AG-041R

gastrin/CCKB receptor antagonist

Preclinical N

NCGC00263122

Nicotinic Acid Receptor Partial Agonist

MK-0354

O=C1[C@](CC(NC2=CC=C(C)C=C2) =O)(NC(NC3=CC=C(C)C=C3)=O)C4= CC=CC=C4N1CC(OCC)OCC 199800-49-2

O HN

HN

N NH N N

N H

Discontinued

C1(NN=C2C3=NNN=N3)=C2CCC1

851776-28-8

HCl N N

NCGC00165875

PB-28

sigma1/2 Receptor Agonist

OMe HCl

COC1=CC=CC2=C1CCCC2CCCN3C CN(C4CCCCC4)CC3.Cl.Cl 172907-03-8

Preclinical N MeO

NCGC00263126

Cutamesine hydrochloride

AGY-94806/SA4503

N HCl

sigma1 Receptor Agonist

Phase II

MeO

HCl

COC(C=C1)=C(OC)C=C1CCN(CC2) CCN2CCCC3=CC=CC=C3.Cl.Cl

165377-44-6

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES N

Cl

N

HBr

BD-1047

sigma Receptor Antagonist

Preclinical HCl

NCGC00025225

SCH-79797

PAR1 Antagonist

NH2

N

N H

Preclinical

NC1=C2C(C=CC3=C2C=CN3CC4=C C=C(C(C)C)C=C4)=NC(NC5CC5)=N1 .Cl.Cl 245520-69-8

N

HCl

N

O

H

H

H

H

H N

O

O

O=C(O[C@@H]1C)[C@@]2([H])[C@] 1([H])[C@@H](/C=C/C3=CC=C(C4=C C=CC(F)=C4)C=N3)[C@@](CC[C@ @H](NC(OCC)=O)C5)([H])[C@]5([H]) C2 618385-01-6

O

N

NCGC00263108

Vorapaxar

MK-5348/SCH530348

PAR1 Antagonist

Phase III

F

O

NCGC00263107

GB 83

PAR2 Antagonist

O=C(N[C@@H](CC1CCCCC1)C(N[C @@H]([C@H](C)CC)C(N2CCC3(C(C =CC=C4)=C4CC3)CC2)=O)=O)C5=C C=NO5 1252806-86-2

O

H N

N H

N O

HBr

ClC1=C(Cl)C=CC(CCN(CCN(C)C)C)= C1.Br.Br 138356-20-4

Cl

NCGC00024901

CAS #

N

O

Preclinical CF3

C[C@H](C1=CC(C(F)(F)F)=CC(C(F)( F)F)=C1)O[C@@H]2[C@H](C3=CC= C(F)C=C3)N(CC(N4)=NNC4=O)CCO 2 170729-80-3

CF3 O

NCGC00181785

Aprepitant

L-754030 /MK0869/ONO-7436

H N

F

O

Tachykinin NK1 Antagonist

HN N

Approved

N

F N H

NCGC00025092

GR-159897

O

N


OS+

MeO

FC1=CC=C(NC=C2CCN3CCC(C[S@ @+](C4=CC=CC=C4)[O])(OC)CC3)C2=C1 158848-32-9

Preclinical O N

N

N

O=C(C1=CC=CC=C1)N2CCC[C@](C CCN3CCC(C4=CC=CC=C4)(N(C(C)= O)C)CC3)(C5=CC=C(Cl)C(Cl)=C5)C2 160492-56-8

O Cl Cl

NCGC00263110

Osanetant

SR-142806


Discontinued O

H N

N O

NCGC00263139

Rolofylline

HMR-4902/KW3902/MK-7418

Adenosine A1 Antagonist

Phase III N N

NCGC00242513

Maraviroc

Selzentry/UK427857/Celsentri

O=C1C2=C(N=C([C@@]3(C(C4)C5) C[C@@H]4CC5C3)N2)N(CCC)C(N1 CCC)=O

N

N

N

N NH

F

CCR5 Antagonist

F

Approved

O

136199-02-5

O=C(N[C@@H](CCN1C2CCC1CC(C 2)n1c(C)nnc1C(C)C)c1ccccc1)C1CC C(F)(F)CC1 376348-65-1

O

O

O

O

NCGC00092385

LY-320135

Cannabinoid CB1 Antagonist

Preclinical

N

N#CC1=CC=C(C(C2=C(C3=CC=C(O C)C=C3)OC4=CC(OC)=CC=C24)=O) C=C1 176977-56-3

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O N H

NCGC00162405

ACPA

cannabinoid CB1 antagonist

CCCCC\C=C/C\C=C/C\C=C/C/C=C\C CCC(NC1CC1)=O 229021-64-1

Preclinical tBu S CO2H

CC(C)C1=CC=C(N(CC2=CC=C(Cl)C =C2)C(CC(C)(C)C(O)=O)=C3SC(C)(C )C)C3=C1 118414-82-7

N

NCGC00025106

MK-886

L-663536

5-lipoxygenase-activating (FLAP) Leukotriene synthesis inhibitor inhibitor/PPAR modulator

Cl

Phase II

CO2H N

NCGC00250411

NCGC00250374

Veliflapon

Licofelone

BAY-X 1004

ML-3000

5-lipoxygenase-activating (FLAP) inhibitor Leukotriene synthesis inhibitor

5-Lipoxygenase Inhibitor

Cyclooxygenase-1 Inhibitor/Cyclooxygenase-2 Inhibitor/Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) Inhibitor

O

O=C([C@H](C1CCCC1)C(C=C2)=CC =C2OCC3=NC4=CC=CC=C4C=C3)O 128253-31-6

Phase III Cl

N

OH

OC(CC1=C(C2=CC=C(Cl)C=C2)C(C3 =CC=CC=C3)=C4N1CC(C)(C)C4)=O 156897-06-2

O

Phase III HO N

NH2 O

S

NCGC00159453

Zileuton

A-64077/ABT-077 5-Lipoxygenase Inhibitor

Leukotriene Synthesis Inhibitor

CC(N(O)C(N)=O)C1=CC2=CC=CC=C 2S1 111406-87-2

Approved

N N

NCGC00187940

15-Lipoxygenase Inhibitor

S

O

S

O

O=C(C1=CC2=C(C=CC=C2)S1)OCC #CCSC3=NN=C(C4=C(C=CC=C5)C5 =CC=C4)O3 1222876-54-1

O

Preclinical O O S

H2N

N N

NCGC00091455

Celecoxib

Cyclooxygenase-2 Inhibitor

Caspase 3 Activator

CF3

NS(C(C=C1)=CC=C1N2C(C3=CC=C( C)C=C3)=CC(C(F)(F)F)=N2)(=O)=O 169590-42-5

Approved OMe

O

N

NCGC00160396

Pravadoline

Win-48098

COX inhibitor and cannabinoid (CB) agonist

N

O=C(C1=CC=C(OC)C=C1)C2=C(C)N (CCN3CCOCC3)C4=CC=CC=C42 92623-83-1

O

Phase II

N

O F3C

NCGC00263131

PF-3845

Fatty Acid Amide Hydrolase (FAAH) Inhibitor

N N

O

Preclinical HO

N

NCGC00164604

Fluvastatin

Approved

O=C(NC1=CC=CN=C1)N(CC2)CCC2 CC3=CC=CC(OC4=NC=C(C(F)(F)F)C =C4)=C3 1196109-52-0

COOH OH

F

SRI-62320/XU-62320 HMG-CoA Reductase Inhibitors

N H

CC(C)N(C(/C=C/[C@@H](O)C[C@H]( CC(O)=O)O)=C1C2=CC=C(F)C=C2) C3=C1C=CC=C3 93957-55-2

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES HO

NCGC00016940

Simvastatin

Zocor, Simlup, Simcard, Simvacor, Simvoget, Zorced HMG-CoA Reductase Inhibitor

CAS #

O O

O O

C[C@@H]1C[C@H](OC(C(C)(C)CC) =O)C2C(C=C[C@H](C)[C@@H]2CC[ C@H]3OC(CC(O)C3)=O)=C1 79902-63-9

Approved O N H

S

CC(C(CC)CC)C1(C(NC2=C(SC(C(C) C)=O)C=CC=C2)=O)CCCCC1 211513-37-0

O

NCGC00263083

Dalcetrapib

CETP Inhibitor

Phase III N N OEt

N

NCGC00263211

JK 184

Alcohol dehydrogenase 7 inhibitor

S

CC1=C(C2=CSC(NC3=CC=C(OCC)C =C3)=N2)N4C=CC=CC4=N1 315703-52-7

N H

Preclinical N N

NCGC00249666

NCGC00037850

HPGD Inhibitor

N

N

CC(N(C1=CC=CC=C1)C(C)=C2)=C2 C3=NN=C4CCCCCN43 380422-12-8

Preclinical O O OH O

NCGC00263222

CAY10581

Indoleamine 2,3-dioxygenase (IDO) inhibitor

HN

O=C1C2=C([C@H](NCC3=CC=CC=C 3)[C@H](O)C(C)(C)O2)C(C4=CC=CC =C41)=O 1018340-07-2

Preclinical O N O

O

NCGC00024631

EBPC

Aldose Reductase Inhibitor

Preclinical O

O

NCGC00263135

Piraxostat

Xanthine Oxidase Inhibitor

OC1=C(C(OCC)=O)CN(C1=O)CC2=C C=CC=C2 57056-57-2

OH

S

Discontinued

OH

N

N O

O N

O=C(OC1=CC=C([N+]([O])=O)C=C1)N2CCC(C(C3=CC(OCO4) =C4C=C3)(O)C5=CC=C(OCO6)C6=C 5)CC2 1101854-58-3

NO2 OH

NCGC00263237

JZL-184

Monoacylglycerol lipase (MAGL) inhibitor

Preclinical

CC(C)(C)COC1=C(C#N)C=C(N2N=C C(C(O)=O)=C2)C=C1 206884-98-2

O

O

O

O

HN N

O N H

H N

NCGC00165782

GW 4869

Neutral Sphingomyelinase (NSMase) Inhibitor

Preclinical

NH

O

O EtO

NH NH2 S

NCGC00263221

Ezatiostat

Glutathione-s-transferase P1 (GSTP1) Inhibitor

O

Phase II

O=C(NC1=CC=C(C2=NCCN2)C=C1)/ C=C/C3=CC=C(/C=C/C(NC4=CC=C( C5=NCCN5)C=C4)=O)C=C3 6823-69-4

O

N

H N

O OEt

O=C(OCC)[C@H](NC([C@@H](NC(C C[C@@H](C(OCC)=O)N)=O)CSCC1 =CC=CC=C1)=O)C2=CC=CC=C2 168682-53-9

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES O

O[C@@H]1[C@H](N2CCCCC2)[C@ @H](CC/C=C\CCC(O)=O)[C@@H](O CC3=CC=C(C4=CC=CC=C4)C=C3)C 1.Cl 87248-13-3

O HO

NCGC00025325

Vapiprost hydrochloride

N OH

GR-32191B

Prostanoid TP Antagonist

CAS #

HCl

Phase III OH OH

NCGC00095134

Ezetimibe

Ezetrol, Zetia, Zient, MK-0653, SCH-58235

NPC1L1 Inhibitor

O=C1[C@H](CC[C@H](O)C2=CC=C( F)C=C2)[C@@H](C3=CC=C(O)C=C3 )N1C4=CC=C(F)C=C4 163222-33-1

N

F

O F

Approved O N N N

NCGC00263281

GSK-1995010

FAS inhibitor

O=C(C1CC1)N(C2)CC[C@H]2CN3C( C4=CC=C(C5=CC=C(OC=C6)C6=C5) C=C4)=NC7=CN=CC=C73 1309805-49-9

O

N

Preclinical

N

O

O N

NCGC00263228

FASN BI

Fatty acid synthase inhibitor

O

Preclinical H N N N

NCGC00263229

GSK837149A


CN(C([C@H]1CC[C@H](NC(CC)=O) C1)=O)C2=CC=C(C3=NC4=C(C=CC= C4)O3)C=C2 1291779-76-4

NH

O S N H O

H N O N S N N O H

O

O=C(NC1=CC=C(S(NC2=NC=CC(C) =N2)(=O)=O)C=C1)NC3=CC=C(S(NC 4=NC(C)=CC=N4)(=O)=O)C=C3 13616-29-0

Preclinical OMe

OH NC N H

Cl

NCGC00263230

FASN MRK


ClC1=C(C#N)C=C2C(NC(C(C3=CC(C 4=CC=CC=C4OC)=CC=C3)=C2O)=O )=C1 910249-49-9

O

Preclinical O N

O N H

NCGC00182868

Daporinad

FK-866, APO-866 NMPRTase Inhibitor

N

Phase II

O=C(N1CCC(CCCCNC(/C=C/C2=CN =CC=C2)=O)CC1)C3=CC=CC=C3 658084-64-1

H N F

O

O

NCGC00263130

cPEPCK inhibitor

cPEPCK inhibitor

O N

N N

CCCCN(C1=C2N=C(CC3=CC=C(NC( C)=O)C=C3)N1)C(N(CC4=C(F)C=CC =C4)C2=O)=O 628279-07-2

N H

Preclinical Br

O

CN(C1=C(C=C(C2NC3=C(C4=C2C(C C(C)(C4)C)=O)C5=CC=CC=C5C=C3) C=C1)Br)C 311795-38-7

N HN

NCGC00263232

GLS968

Glutaminase inhibitor

Preclinical NH2

NCGC00263233

IPFK2

Inducible phosphofructokinase-2 inhibitor

N H

Preclinical

O

NC1=CC=C(C(C2=CC3=C(C=CC4=C C=CC=C34)N2)=O)C=C1 1332307-32-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

O S

S N N

N

NCGC00186528

NCGC00186528

PKM2 activator

NH2

O

Preclinical

O S N O

O

O N S O

O

NCGC00185916

NCGC00185916

PKM2 activator

NH2

Preclinical O

H HO N

N

NCGC00250391

Pyruvate Dehydrogenase Kinase 2 Inhibitor

AZD-7545

CF3

O

Cl

S O O

Preclinical

CN(C1=C2C=NN(CC3=CC(N)=CC=C 3)C1=O)C4=C2SC(S(C)=O)=C4 1221186-53-3

O=S(N1CCCN(S(=O)(C2=CC=CC(N) =C2)=O)CC1)(C3=CC(OCCO4)=C4C =C3)=O 1203494-49-8 C[C@H](/C=C/C=C/C(CC)(CC)O)[C@ @]1([H])CC[C@@]2([H])/C(CCCC21 C)=C/C=C3C[C@@H](O)C[C@H](O) C\3=C 252017-04-2

OH

O

OH

NCGC00263231

Pyruvate dehydrogenase kinases inhibitor

PDHK RIKEN

OC1=CC(O)=CC=C1C2=NNC(C)=C2 C3=CC=C(C=C3)OC 394237-61-7

N N H

Preclinical

NH O S O

CCCCC1=CC=C(C=C1)NS(=O)(C2= CC=C(C(C(N3CCN(C4=CC=CC(C)=C 4C)CC3)=O)=C2)C)=O 730970-25-9

N

NCGC00263234

Isocitrate dehydrogenase inhibitor

IDH-001

N O

Preclinical O

O

O N

OH

N

NCGC00250392

AR-C155858

MCT1 inhibitor

O=C1C2=C(SC(CC3=C(C)NN=C3C)= C2C(N4C[C@H](O)CO4)=O)N(CC(C) C)C(N1C)=O 496791-37-8

S

N

O

N H

Preclinical

N

NH2 H N

O O NH

H2N O O

O=C([C@H](NC([C@H](CC1=CC=C(O)C=C1) NC2=O)=O)CC3=CNC4=CC=CC=C43)N[C@ @H](CCCCN)C(N[C@H](C(N[C@H](C(N)=O)C (O)C)=O)CSSC[C@@H]2CC([C@H](N)CC5=C C=CC=C5)=O)=O

OH NH

HN NH

HN O

NCGC00250393

Somatostatin srif2B (sst4) Agonist

CAP-232

S S

O

HO

NH2 O

Phase II

147159-51-1

O HN O

NCGC00263235

ACC1 BMS

Acetyl-CoA carboxylase inhibitor

O H2N

NCGC00263115

Ibutamoren mesilate

L-163191/MK0677

Growth Hormone Secretagogue

CC(OC1=CC=C(C=C1)OC2=CC=C(C (NC(C)=O)C)C=C2)C

O

Preclinical

O N S O

O N H

N O

O O S OH

Phase III

O=C(N[C@H](COCC1=CC=CC=C1)C (N2CCC3(CN(S(C)(=O)=O)C4=C3C= CC=C4)CC2)=O)C(C)(C)N.CS(O)(=O) =O 159752-10-0

MeO N N

H2NO2S

NCGC00263209

ML 141

Cdc42 GTPase inhibitor

Preclinical

O=S(C(C=C1)=CC=C1N2N=C(C3=C C=CC=C3)CC2C4=CC=C(OC)C=C4)( N)=O 71203-35-5

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure

SMILES

CAS #

Ph OH

HN

NCGC00263207

ADO-ribosylation factor GTPase activating protein 1 inhibitor

QS11

Wnt/b-catenin synergist

OC[C@H](CC1=CC=CC=C1)NC2=N C(OC3=CC4=C(CCC4)C=C3)=NC5= C2N=CN5CC6=CC=C(C7=CC=CC=C 7)C=C6 1217444-15-9

N

N

N

N

O

Preclinical H N

O Cl

ClC1=C2C(NC(C([O])=O)=C2/C=C/C(NC3=CC=CC=C3)= O)=CC(Cl)=C1.[Na+] 153436-38-5

O

NCGC00263106

Gavestinel sodium GV-150526A

NMDA Glycine-Site Antagonist

O- Na+

N H

Cl

Phase III OH

N

F

Cl

NCGC00092329

Eliprodil

SL-82.0715

NMDA Antagonist

ClC1=CC=C(C(CN2CCC(CC3=CC=C (F)C=C3)CC2)O)C=C1 119431-25-3

Phase III HCl N

N N

NCGC00186046

Caroverine hydrochloride

O

Spasmium

AMPA Antagonist

O

O N N HN

O O

NCGC00263113

GYKI-53655

LY-300168

CCN(CCN1C(C(CC2=CC=C(C=C2)O C)=NC3=CC=CC=C13)=O)CC.Cl 55750-05-5

Approved

AMPA receptor antagonist

CC1N(C(NC)=O)N=C(C2=CC=C(N)C =C2)C3=CC4=C(OCO4)C=C3C1 143692-18-6

H2N

Preclinical

OEt

Cl O

HO HO

NCGC00250402

Dapagliflozin

BMS-512148

SGLT-2 inhibitor

O[C@@H]1[C@@H](CO)O[C@@H]( C2=CC(CC3=CC=C(OCC)C=C3)=C( Cl)C=C2)[C@H](O)[C@H]1O 461432-26-8

OH OH

Phase III

Cl

-

O N+

S

N O

O

O=C(OC(C)(C)C)CN(CC1=CC=C(Cl) C=C1)CC2=CC=C([N+]([O-])=O)S2 1216744-19-2

O

NCGC00242476

GSK-4112

SR-6452

Rev-erb alpha agonist

Preclinical N O

N

N N+

NCGC00242514

Sepantronium bromide

O

O Br-

YM-155

Survivin inhibitor

BIRC5 Expression Inhibitor

Phase II

O=C1C2C([n+](CCOC)c(C)n2CC3=N C=CN=C3)C(C4=CC=CC=C41)=O.[Br] 781661-94-7

O HO HN

NCGC00242492

BIBR 1532

BIBR-1532

Telomerase Inhibitor

C/C(C1=CC2=CC=CC=C2C=C1)=C\C (NC3=C(C(O)=O)C=CC=C3)=O 321674-73-1

O

Preclinical S N

N

N

NCGC00242501

ITX3

Triple Functional Domain Protein (TRIO) Inhibitor

O

Preclinical

CC1=C(/C=C2SC3=NC(C=CC=C4)=C 4N3C\2=O)C=C(C)N1C5=CC=CC=C5 347323-96-0

NCGC ID

Name

Alias

Primary Mechanism


Phase

Structure O HO O H O

O

HO

NCGC00168477

Salinomycin

Procoxacin

Efavirenz

Stocrin, Sustiva, DMP-266, L743726

Anticoccidial/Antibacterial

H

OH O

O

O

HO

H

H

Preclinical

SMILES

CAS #

CC[C@@]1(O)CC[C@@]([C@@]2(C)O[C@@ ]3([C@H](O)C=C[C@]4(O[C@@]([C@@H](CC )C([C@@H](C)[C@@H](O)[C@H](C)[C@@]5( [H])[C@@H](C)CC[C@@]([C@@H](CC)C(O)= O)([H])O5)=O)([H])[C@@H](C)C[C@H]4C)O3) CC2)([H])O[C@H]1C

53003-10-4

F3C

NCGC00159337

Cl

Reverse Transcriptase Inhibitor

O N H

Approved

ClC1=CC=C(NC(OC2(C#CC3CC3)C( F)(F)F)=O)C2=C1 154598-52-4

O

OAc O

N

O O S N O

NCGC00167805

Ivachtin

Caspase 3 inhibitor

OH

O=C(N/N=C/C1=C(O)C(CC=C)=CC= C1)CN(CC2)CCN2CC3=CC=CC=C3 315183-21-2

O N

PAC-1

O=S(C1=CC=C(N=C(C)C(C(N2CCOC (C)=O)=O)=C3C2=O)C3=C1)(N4CCO CC4)=O 745046-84-8

Preclinical N

NCGC00167785

O N

Procaspase 3 Activator

N H

N

Preclinical O N S

N H

NCGC00092372

Necrostatin-1

RIP Kinase inhibitor

Indoleamine 2,3-dioxygenase Inhibitor

O=C(N(C)C(N1)=S)C1CC2=CNC3=C 2C=CC=C3 4311-88-0

N H

Preclinical F3C

O

O

O

OH

NCGC00263142

Tiplasinin

PAI-039

Plasminogen Activator Inhibitor (PAI-1) Inhibitor

N

Phase I H

H O

O

O

NCGC00263265

ASR-isobudimerSO2Ph-4-

ASR-isobudimerSO2Ph-4-

CH2OC(O)NMe2

CH2OC(O)NMe2

O O

O

N

O S O

O H O

artemesinin analogue

Preclinical

O O H

O O

O

O

NCGC00263268

BTM-2C-dimer ketone

BTM-2C-dimer ketone

OH

O O

O O

H

H H


Preclinical O N

O O

NCGC00263270

BTM-2C-dimer allyl BTM-2C-dimer oxime allyl oxime

H

O OH

O

O

O

O H


Preclinical

H

O=C(C(O)=O)C1=CN(CC2=CC=CC= C2)C(C1=C3)=CC=C3C4=CC=C(OC( F)(F)F)C=C4 393105-53-8 C[C@](O1)(OO2)CC[C@]3([H])[C@]2([C@@H ]1O[C@H](CC(CS(C4=CC=C(COC(N(C)C)=O) C=C4)(=O)=O)C[C@H]5O[C@H]6[C@@]78[C @](CC[C@](C)(OO8)O6)([H])[C@H](C)CC[C@ @]7([H])[C@H]5C)[C@@H]9C)[C@@]9([H])C C[C@H]3C

1123339-60-5

C[C@](O1)(OO2)CC[C@]3([H])[C@]2([C@@H ]1O[C@H](CC([C@H]4O[C@H]5[C@@]67[C@ ](CC[C@](C)(OO7)O5)([H])[C@H](C)CC[C@@ ]6([H])[C@H]4C)=O)[C@@H]8C)[C@@]8([H]) CC[C@H]3C

NA

C[C@](O1)(OO2)CC[C@]3([H])[C@]2([C@@H ]1O[C@H](C/C([C@H]4O[C@H]5[C@@]67[C @](CC[C@](C)(OO7)O5)([H])[C@H](C)CC[C@ @]6([H])[C@H]4C)=N/OCC=C)[C@@H]8C)[C @@]8([H])CC[C@H]3C

NA

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