Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine
Open accessAbstract
SRC is a major regulator of many signaling pathways and contributes to cancer development. However, development of a selective SRC inhibitor has been challenging, and FDA-approved SRC inhibitors, dasatinib and bosutinib, are multitargeted kinase inhibitors. Here, we describe our efforts to develop a selective SRC covalent inhibitor by targeting cysteine 277 on the P-loop of SRC. Using a promiscuous covalent kinase inhibitor (CKI) SM1-71 as a starting point, we developed covalent inhibitor 15a, which discriminates SRC from other covalent targets of SM1-71 including TAK1 and FGFR1. As an irreversible covalent inhibitor, compound 15a exhibited sustained inhibition of SRC signaling both in vitro and in vivo . Moreover, 15a exhibited potent antiproliferative effects in nonsmall cell lung cancer cell lines harboring SRC activation, thus providing evidence that this approach may be promising for further drug development efforts.
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DGY-06-116 targets cysteine-277 in the P-loop.
“We also demonstrated that an irreversible covalent inhibitor of SRC, DGY-06-116, which targets cysteine-277 in the P-loop (49, 50), enhances the antitumor activity of MRTX849 in multiple KRAS-G12C cancers.”
From SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition (2024) · cites this paper as [49]
The Mass Spectrometry methods describe treating SRC with DGY-06–116 and searching for cysteine modification. The Results section identifies Cys277 in the P-loop as the modification site for compound 15a, but the passages do not establish that 15a is DGY-06–116 or report DGY-06–116’s modification site. (LLM, conf=0.78)
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Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621 · see citing works
Cellular functions regulated by Src family kinases.
Thomas, S. M., & Brugge, J. (1997) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.13.1.513 · Cited by 2,610 · see citing works
Discovery and development of sorafenib: a multikinase inhibitor for treating cancer
Wilhelm, S. M., Carter, C., Lynch, M. J., Lowinger, T. B., Dumas, J., Smith, R. A., Schwartz, B. E., Simantov, R., & Kelley, S. L. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2130 · Cited by 1,826 · see citing works
Kinase inhibitors: the road ahead
Ferguson, F. M., & Gray, N. S. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.21 · Cited by 1,009 · see citing works
Self-citationRole of Src expression and activation in human cancer
Irby, R., & Yeatman, T. J. (2000) · Oncogene · doi:10.1038/sj.onc.1203912 · Cited by 856 · see citing works
Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs
Hafner, M., Niepel, M., Chung, M., & Sorger, P. K. (2016) · Nature Methods · doi:10.1038/nmeth.3853 · Cited by 681 · see citing works
Self-citationRix, U., Hantschel, O. D., Dürnberger, G., Rix, L. L. R., Planyavsky, M., Fernbach, N. V., Kaupe, I., Bennett, K. L., Valent, P., Colinge, J., et al. (2007) · Blood · doi:10.1182/blood-2007-07-102061 · Cited by 673 · see citing works
Developing Irreversible Inhibitors of the Protein Kinase Cysteinome
Liu, Q., Sabnis, Y. A., Zhao, Z., Zhang, T., Buhrlage, S. J., Jones, L. H., & Gray, N. S. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.12.006 · Cited by 662 · see citing works
Self-citationProperties of FDA-approved small molecule protein kinase inhibitors
Roskoski, R. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.03.006 · Cited by 554 · see citing works
Docking Covalent Inhibitors: A Parameter Free Approach To Pose Prediction and Scoring
Zhu, K., Borrelli, K., Greenwood, J., Day, T., Abel, R., Farid, R., & Harder, E. D. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci500118s · Cited by 445 · see citing works
Das, J., Chen, P., Norris, D. J., Padmanabha, R., Lin, J., Moquin, R. V., Shen, Z., Cook, L. S., Doweyko, A. M., Pitt, S., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060727j · Cited by 399 · see citing works
Hennequin, L. F., Allen, J. M., Breed, J., Curwen, J., Fennell, M., Green, T. P., der Brempt, C. L., Morgentin, R., Norman, R. A., Olivier, A., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060434q · Cited by 365 · see citing works
The Role of Src in Solid Tumors
Wheeler, D. L., Iida, M., & Dunn, E. F. (2009) · The Oncologist · doi:10.1634/theoncologist.2009-0009 · Cited by 346 · see citing works
Targeting Src family kinases in anti-cancer therapies: turning promise into triumph
Zhang, S., & Yu, D. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.11.002 · Cited by 323 · see citing works
Global target profile of the kinase inhibitor bosutinib in primary chronic myeloid leukemia cells
Rix, L. L. R., Rix, U., Colinge, J., Hantschel, O. D., Bennett, K. L., Stranzl, T., Müller, A. C., Baumgärtner, C., Valent, P., Augustin, M. A., et al. (2008) · Leukemia · doi:10.1038/leu.2008.334 · Cited by 284 · see citing works
Lu, Y., Yu, Q., Liu, J. H., Zhang, J., Wang, H., Koul, D., McMurray, J. S., Fang, X., Yung, W. K. A., Siminovitch, K. A., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303621200 · Cited by 262 · see citing works
Targeting Src in breast cancer
Finn, R. S. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn291 · Cited by 248 · see citing works
Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530
Green, T. P., Fennell, M., Whittaker, R., Curwen, J., Jacobs, V., Allen, J., Logie, A., Hargreaves, J., Hickinson, D. M., Wilkinson, R. W., et al. (2009) · Molecular Oncology · doi:10.1016/j.molonc.2009.01.002 · Cited by 238 · see citing works
Regulation of Src Family Kinases in Human Cancers
Sen, B., & Johnson, F. M. (2011) · Journal of Signal Transduction · doi:10.1155/2011/865819 · Cited by 231 · see citing works
Papaetis, G. S., & Syrigos, K. (2009) · BioDrugs · doi:10.2165/11318860-000000000-00000 · Cited by 225 · see citing works
López-Ocejo, O., Viloria‐Petit, A., Béquet‐Romero, M., Mukhopadhyay, D., Rak, J. W., & Kerbel, R. S. (2000) · Oncogene · doi:10.1038/sj.onc.1203817 · Cited by 218 · see citing works
Optimization of 4-Phenylamino-3-quinolinecarbonitriles as Potent Inhibitors of Src Kinase Activity
Boschelli, D. H., Ye, F., Wang, Y. D., Dutia, M. D., Johnson, S. L., Wu, B., Miller, K., Powell, D. W., Yaczko, D., Young, M., et al. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0102250 · Cited by 218 · see citing works
Activity‐based kinase profiling of approved tyrosine kinase inhibitors
Kitagawa, D., Yokota, K., Gouda, M., Narumi, Y., Ohmoto, H., Nishiwaki, E., Akita, K., & Kirii, Y. (2012) · Genes to Cells · doi:10.1111/gtc.12022 · Cited by 202 · see citing works
Lai, S., & Johnson, F. (2010) · Drug resistance updates · doi:10.1016/j.drup.2010.04.001 · Cited by 190 · see citing works
Tan, L., Wang, J., Tanizaki, J., Huang, Z., Aref, A. R., Rusan, M., Zhu, S.-J., Zhang, Y., Ercan, D., Liao, R. G., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1403438111 · Cited by 178 · see citing works
Self-citationBoland, J. M., Erdogan, S., Vasmatzis, G., Yang, P., Tillmans, L. S., Johnson, M. R., Wang, X., Peterson, L. M., Halling, K. C., Oliveira, A. M., et al. (2009) · Human Pathology · doi:10.1016/j.humpath.2009.01.012 · Cited by 171 · see citing works
SRC gene expression in human cancer: the role of transcriptional activation
Dehm, S. M., & Bonham, K. (2004) · Biochemistry and Cell Biology · doi:10.1139/o03-077 · Cited by 165 · see citing works
Current status of SRC inhibitors in solid tumor malignancies
Puls, L. N., Eadens, M., & Messersmith, W. (2011) · The Oncologist · doi:10.1634/theoncologist.2010-0408 · Cited by 158 · see citing works
Zhang, J., Kalyankrishna, S., Wislez, M., Thilaganathan, N., Saigal, B., Wei, W., Ma, L., Wistuba, I. I., Johnson, F. M., & Kurie, J. M. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060706 · Cited by 154 · see citing works
Development of a Highly Selective c-Src Kinase Inhibitor
Brandvold, K. R., Steffey, M. E., Fox, C. C., & Soellner, M. B. (2012) · ACS Chemical Biology · doi:10.1021/cb300172e · Cited by 127 · see citing works
GRcalculator: an online tool for calculating and mining dose–response data
Clark, N. A., Hafner, M., Kouril, M., Williams, E. H., Muhlich, J. L., Pilarczyk, M., Niepel, M., Sorger, P. K., & Medvedovic, M. (2017) · BMC Cancer · doi:10.1186/s12885-017-3689-3 · Cited by 121 · see citing works
Self-citationSrc as a potential therapeutic target in non-small-cell lung cancer
Giaccone, G., & Zucali, P. A. (2008) · Annals of Oncology · doi:10.1093/annonc/mdn048 · Cited by 99 · see citing works
c-Src modulates ErbB2 and ErbB3 heterocomplex formation and function
Ishizawar, R. C., Miyake, T., & Parsons, S. J. (2006) · Oncogene · doi:10.1038/sj.onc.1210138 · Cited by 96 · see citing works
Sánchez-Bailón, M. P., Calcabrini, A., Gómez-Domínguez, D., Morte, B., Martín-Forero, E., Goméz-López, G., Molinari, A., Wagner, K., & Martı́n-Pérez, J. (2012) · Cellular Signalling · doi:10.1016/j.cellsig.2012.02.011 · Cited by 76 · see citing works
Fraser, C., Dawson, J. C., Dowling, R., Houston, D. R., Weiss, J. T., Munro, A. F., Muir, M., Harrington, L. A., Webster, S. P., Frame, M. C., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00065 · Cited by 76 · see citing works
Leveraging Compound Promiscuity to Identify Targetable Cysteines within the Kinome
Rao, S., Gurbani, D., Du, G., Everley, R. A., Browne, C. M., Chaikuad, A., Tan, L., Schröder, M., Gondi, S. R., Ficarro, S. B., et al. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.02.021 · Cited by 67 · see citing works
Self-citationTintori, C., Fallacara, A. L., Radi, M., Zamperini, C., Dreassi, E., Crespan, E., Maga, G., Schenone, S., Musumeci, F., Brullo, C., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5013159 · Cited by 63 · see citing works
Zhang, C., Zheng, M.-W., Li, Y., Lin, X., Huang, M. J., Zhong, L., Li, G., Zhang, R.-J., Lin, W.-T., Jiao, Y., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00270 · Cited by 50 · see citing works
Huang, W., Zhu, X., Wang, Y., Azam, M., Wen, D. J., Sundaramoorthi, R., Thomas, R. M., Liu, S., Banda, G., Lentini, S. P., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm900166t · Cited by 49 · see citing works
Irreversible Inhibitors of c-Src Kinase That Target a Nonconserved Cysteine
Kwarcinski, F. E., Fox, C. C., Steffey, M. E., & Soellner, M. B. (2012) · ACS Chemical Biology · doi:10.1021/cb300337u · Cited by 45 · see citing works
Exploiting the promiscuity of imatinib
Lee, S. J., & Wang, J. Y. J. (2009) · Journal of Biology · doi:10.1186/jbiol134 · Cited by 45 · see citing works
Formisano, L., D'Amato, V., Servetto, A., Brillante, S., Raimondo, L., Mauro, C. D., Marciano, R., Orsini, R. C., Cosconati, S., Randazzo, A., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4636 · Cited by 42 · see citing works
Maa, M. C., Leu, T., Trandel, B. J., Chang, J. H., & Parsons, S. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.8.5466 · Cited by 40 · see citing works
Ficarro, S. B., Browne, C. M., Card, J. D., Alexander, W. M., Zhang, T., Park, E., McNally, R., Dhe‐Paganon, S., Seo, H., Lamberto, I., et al. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.6b03394 · Cited by 37 · see citing works
Self-citationProfile of bosutinib and its clinical potential in the treatment of chronic myeloid leukemia
Koschmieder, S., & Keller-v.Amsberg (2013) · OncoTargets and Therapy · doi:10.2147/ott.s19901 · Cited by 36 · see citing works
Structure-guided development of covalent TAK1 inhibitors
Tan, L., Gurbani, D., Weisberg, E., Hunter, J. C., Li, L., Jones, D. S., Ficarro, S. B., Mowafy, S., Tam, C. P., Rao, S., et al. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.11.035 · Cited by 33 · see citing works
Self-citationActivation of Src signaling mediates acquired resistance to ALK inhibition in lung cancer
Yoshida, R., Sasaki, T., Minami, Y., Hibino, Y., Okumura, S., Sado, M., Miyokawa, N., Hayashi, S., Kitada, M., & Ohsaki, Y. (2017) · International Journal of Oncology · doi:10.3892/ijo.2017.4140 · Cited by 29 · see citing works
Trastuzumab resistance: all roads lead to SRC
Muthuswamy, S. K. (2011) · Nature Medicine · doi:10.1038/nm0411-416 · Cited by 27 · see citing works
Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors
Tan, L., Gurbani, D., Weisberg, E., Jones, D. S., Rao, S., Singer, W. D., Bernard, F., Mowafy, S., Jenney, A., Du, G., et al. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.11.034 · Cited by 22 · see citing works
Self-citationLiang, X., Liu, X., Wang, B., Zou, F., Wang, A., Qi, S., Chen, C., Zhao, Z., Wang, W., Qi, Z., et al. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01618 · Cited by 19 · see citing works
A multitargeted probe-based strategy to identify signaling vulnerabilities in cancers
Rao, S., Du, G., Hafner, M. A., Subramanian, K., Sorger, P. K., & Gray, N. S. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.006805 · Cited by 12 · see citing works
Self-citationMaa, M., Leu, T., Trandel, B. J., Chang, J., & Parsons, S. J. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.8.5466-5473.1994 · Cited by 10 · see citing works
Flagged first, then by citations
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Sorted by citations
Kuljanin, M., Mitchell, D. C., Schweppe, D. K., Gikandi, A. S., Nusinow, D. P., Bulloch, N. J., Vinogradova, E. V., Wilson, D. L., Kool, E. T., Mancias, J. D., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-00778-3 · Cited by 305 · see citing works
Discovery of Cysteine-targeting Covalent Protein Kinase Inhibitors
Lu, X., Smaill, J. B., Patterson, A. V., & Ding, K. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01719 · Cited by 146 · see citing works
The vinyl sulfone motif as a structural unit for novel drug design and discovery
Xiao, Y., & Chen, F. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2284201 · Cited by 48 · see citing works
Zhang, Y., Zhang, T., Tu, S., Zhang, Z., & Meng, F. (2020) · Molecules · doi:10.3390/molecules25184094 · Cited by 47 · see citing works
Self-citationZhang, Q., Chen, X., Cao, J., Yang, W., Wan, G., Feng, Q., Zhou, S., Yang, H., Wang, N., Liu, Z., et al. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01370 · Cited by 35 · see citing works
Structure and Characterization of a Covalent Inhibitor of Src Kinase
Gurbani, D., Du, G., Henning, N. J., Rao, S., Bera, A. K., Zhang, T., Gray, N. S., & Westover, K. D. (2020) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2020.00081 · Cited by 29 · see citing works
Self-citationStructural insights into redox-active cysteine residues of the Src family kinases
Heppner, D. E. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101934 · Cited by 29 · see citing works
Dong, Y., Lu, J., Zhang, S., Chen, L., Wen, J., Wang, F., Mao, Y., Li, L., Zhang, J., Liao, S., et al. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106446 · Cited by 28 · see citing works
SRC kinase drives multidrug resistance induced by KRAS-G12C inhibition
Song, X., Zhou, Z., Elmezayen, A., Wu, R., Yu, C., Gao, B., Minna, J. D., Westover, K. D., Zeh, H. J., Kroemer, G., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq4274 · Cited by 26 · see citing works
Self-citationWen, W., Cao, H., Huang, Y., Tu, J., Chen, W., Wan, J., Han, X., Chen, H., Liu, J., Rao, L., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c02102 · Cited by 22 · see citing works
Brawn, R. A., Cook, A. S., Omoto, K., Ke, J., Karr, C. D., Colombo, F., Virrankoski, M., Prajapati, S., Reynolds, D. J., Bolduc, D. M., et al. (2020) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.0c00517 · Cited by 19 · see citing works
Dynamics of Post-Translational Modification Inspires Drug Design in the Kinase Family
Zhang, H., He, J., Hu, G., Zhu, F., Jiang, H., Gao, J., Zhou, H., Lin, H., Wang, Y., Chen, K., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01076 · Cited by 19 · see citing works
Teli, G., Pal, R., Maji, L., Matada, G. S. P., & Sengupta, S. (2023) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2023.2205943 · Cited by 18 · see citing works
Recent advances of small-molecule c-Src inhibitors for potential therapeutic utilities
Dang, X., Duan, J., Ye, E., Mao, N.-D., Bai, R., Zhou, X., & Ye, X. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106934 · Cited by 18 · see citing works
Emerging Roles of YES1 in Cancer: The Putative Target in Drug Resistance
Kook, E., Chun, K., & Kim, D. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031450 · Cited by 18 · see citing works
Drug resistance and tumor heterogeneity: cells and ensembles
Nussinov, R., Yavuz, B. R., & Jang, H. (2025) · Biophysical Reviews · doi:10.1007/s12551-025-01320-y · Cited by 17 · see citing works
Discovery of Covalent Ligands with AlphaFold3
Shamir, Y., Gabizon, R., Rogel, A., Lin, D. Y.-W., Andreotti, A. H., & London, N. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.5c22222 · Cited by 17 · see citing works
Teli, G., Pal, R., Maji, L., Sengupta, S., Raghavendra, N. M., & Matada, G. S. P. (2023) · Chemistry & Biodiversity · doi:10.1002/cbdv.202300515 · Cited by 17 · see citing works
Lau, V., Nurkolis, F., Park, M. N., Heriyanto, D. S., Taslim, N. A., Tallei, T. E., Permatasari, H. K., Tjandrawinata, R. R., Moon, S., & Kim, B. (2024) · Marine Drugs · doi:10.3390/md22060272 · Cited by 17 · see citing works
Dustin, C. M., Habibovic, A., Hristova, M., Schiffers, C., Morris, C. R., Lin, M.-C. J., Bauer, R. A., Heppner, D. E., Daphtary, N., Aliyeva, M., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2000995 · Cited by 16 · see citing works
Zhang, L., Xu, J., Guo, J., Wang, Y., & Wang, Q. (2023) · Molecules · doi:10.3390/molecules28155846 · Cited by 10 · see citing works
Cui, Y., Zhang, J., & Zhang, G. (2023) · Current Medicinal Chemistry · doi:10.2174/0929867330666230622142505 · Cited by 9 · see citing works
A renaissance for YES in cancer
Lapouge, M., & Meloche, S. (2023) · Oncogene · doi:10.1038/s41388-023-02860-x · Cited by 8 · see citing works
SRC at the Crossroads of KRAS Inhibitor Resistance: Mechanisms and Therapeutic Opportunities
Tian, H., Zhao, D., Zhou, Z., Kim, A., Huang, H., Lee, Y. J., Qu, Z., Kang, R., Zeh, H. J., Westover, K. D., et al. (2026) · Cancer Letters · doi:10.1016/j.canlet.2025.218194 · Cited by 7 · see citing works
Self-citationDiscovery of a Covalent Inhibitor Selectively Targeting the Autophosphorylation Site of c-Src Kinase
Zhang, H., Xu, D., Huang, H., Jiang, H., Hu, L., Liu, L., Sun, G., Gao, J., Li, Y., Xia, C., et al. (2024) · ACS Chemical Biology · doi:10.1021/acschembio.4c00048 · Cited by 4 · see citing works
Yan, L., Liu, L., Wang, Q. L., Rao, N. G. R., & Le, Y. (2022) · Heterocycles · doi:10.3987/com-21-14594 · Cited by 4 · see citing works
Ai, Y., Xu, S., Zhang, Y., Liu, Z., & Liu, S. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c03191 · Cited by 3 · see citing works
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Patteson, J. B., Manolaridis, I., Hong, M. R., Johnston, J. M., Mesbahi‐Vasey, S., Gregory, M. C., Iwamoto, D. V., Reid, J. C., Sanders, J. M., Lovatt, D., et al. (2026) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2026.113322 · Cited by 2 · see citing works
Meyer, C. J., McCoy, M. K., Li, L., Posner, B. A., & Westover, K. D. (2023) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2023.101599 · Cited by 2 · see citing works
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Dash, R. P., Thomas, J. A., Rosenfeld, C. A., & Srinivas, N. R. (2020) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-020-00619-3 · Cited by 2 · see citing works
Helmold, B., Ahrens, A., Fitzgerald, Z. B., & Özdi̇nler, P. H. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-02068 · Cited by 1 · see citing works
Yekeen, A. A., Meyer, C. J., McCoy, M. K., Posner, B. A., & Westover, K. D. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5c02430 · Cited by 1 · see citing works
Self-citationRecent updates on c-Src kinase and Src-Abl nonreceptor tyrosine kinases inhibitors
Navneesh, Pandey, S., Shakya, R., Pasricha, S., Kurmi, B. D., & Patel, P. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-96121-9.00005-x · Cited by 1 · see citing works
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Blaney, J., & Davis, A. M. (2023) · Royal Society of Chemistry eBooks · doi:10.1039/9781788018982-00137
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Marino, K. A., Nicewonger, R., Zhang, H., & Thorarensen, A. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00010-8
Redundant roles of YES and SRC tyrosine kinases in driving malignant peripheral nerve sheath tumorsPreprint
Zereg, E., Voisin, L., Courcelles, M., Brochu, S., Gombos, M., Bonneil, É., Grenier, K., Jung, S., Perreault, C., Tirode, F., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.17.706384
Xue, J., Xue, J., You, Y., Lu, J., Zhang, H., Wang, K., Yang, Z., Wang, J., & Deng, Y. (2026) · New Journal of Chemistry · doi:10.1039/d6nj02257j
BindingDB (2023) · UC San Diego · doi:10.7270/q2b85d0b
BindingDB Entry 50015722: Discovery of Cysteine-targeting Covalent Protein Kinase Inhibitors.
BindingDB (2023) · UC San Diego · doi:10.7270/q2hq43wx
- Authors
- Du, G., Rao, S., Gurbani, D., Henning, N. J., Jiang, J., Che, J., Yang, A., Ficarro, S. B., Marto, J. A., Aguirre, A. J., Sorger, P. K., Westover, K. D., Zhang, T., & Gray, N. S.
- Affiliations
- Harvard University (US)
- The University of Texas Southwestern Medical Center (US)
- Dana-Farber Cancer Institute (US)
- Corresponding author
- Westover, Kenneth D.
- Zhang, Tinghu
- Gray, Nathanael S.
- ORCID
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-01-14
- Volume
- 63
- Issue
- 4
- Pages
- 1624-1641
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- PMC
- PMC7493195
- OpenAlex
- W2998780337
- Cited by
- 39
- References
- 52
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 8 · 2023: 11 · 2022: 2 · 2021: 5 · 2020: 4
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Journal of Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA07090720)
- Welch Foundation (I-1829)
- American Cancer Society (RSG-18-039-01-DMC)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- Src kinase, covalent kinase inhibitors, dasatinib, bosutinib, kinase selectivity, TAK1, FGFR1, irreversible inhibition, non-small cell lung cancer, antiproliferative activity, structure-based drug design
- MeSH terms
- AAA Domain, Amino Acid Sequence, Anilides, Animals, Cysteine, Drug Screening Assays, Antitumor, Humans, Mice, Inbred C57BL, Pyrimidines, Structure-Activity Relationship, Drug Design, Molecular Structure, Signal Transduction, src-Family Kinases, Cell Line, Tumor, Protein Kinase Inhibitors, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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