Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies
Abstract
Drugs that covalently bond to their biological targets have a long history in drug discovery. A look at drug approvals in recent years suggests that covalent drugs will continue to make impacts on human health for years to come. Although fraught with concerns about toxicity, the high potencies and prolonged effects achievable with covalent drugs may result in less-frequent drug dosing and in wide therapeutic margins for patients. Covalent inhibition can also dissociate drug pharmacodynamics (PD) from pharmacokinetics (PK), which can result in desired drug efficacy for inhibitors that have short systemic exposure. Evidence suggests that there is a reduced risk for the development of resistance against covalent drugs, which is a major challenge in areas such as oncology and infectious disease.
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Covalent inhibitors have the advantage of sustained inhibition and a longer residence time compared to non-covalent inhibitors because the covalently bound target is continuously inhibited until protein degradation and regeneration.
“Hence, covalent inhibitors have the advantage of sustained inhibition and a longer residence time compared to non-covalent inhibitors because the covalently bound target is continuously inhibited until protein degradation and regeneration.28”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [28]
Covalent inhibitors bind to amino acid residues of target proteins through covalent bonds formed by mildly reactive functional groups to confer additional affinity compared to non-covalent inhibitors.
“Covalent inhibitors, also known as irreversible inhibitors, are a class of inhibitors that bind to amino acid residues of target proteins through covalent bonds formed by mildly reactive functional groups to confer additional affinity, compared to that of non-covalent inhibitors, which achieve binding and inhibition of target proteins through non-covalent interactions such as hydrogen bond and van”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [28]
Cites
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167 · see citing works
A systematic review of the associations between dose regimens and medication compliance
Claxton, A. J., Cramer, J., & Pierce, C. (2001) · Clinical Therapeutics · doi:10.1016/s0149-2918(01)80109-0 · Cited by 2,388 · see citing works
The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP
Yun, C.-H., Mengwasser, K. E., Toms, A. V., Woo, M. S., Greulich, H., Wong, K.-K., Meyerson, M., & Eck, M. J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709662105 · Cited by 2,118 · see citing works
The resurgence of covalent drugs
Singh, J., Petter, R. C., Baillie, T. A., & Whitty, A. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3410 · Cited by 1,873 · see citing works
Identifying and Characterizing Binding Sites and Assessing Druggability
Halgren, T. A. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci800324m · Cited by 1,771 · see citing works
Honigberg, L. A., Smith, A. M., Sirisawad, M., Verner, E., Loury, D., Chang, B., Li, S., Pan, Z., Thamm, D. H., Miller, R. A., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1004594107 · Cited by 1,561 · see citing works
ACETAMINOPHEN-INDUCED HEPATIC NECROSIS. II. ROLE OF COVALENT BINDING IN VIVO
Jollow, D. J., Mitchell, J. R., Potter, W. Z., Davis, D. C., Gillette, J. R., & Brodie, B. B. (1973) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)29664-1 · Cited by 1,203 · see citing works
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155 · see citing works
Acetaminophen-Induced Hepatic Necrosis
Jollow, D. J., Thorgeirsson, S. S., Potter, W. Z., Hashimoto, M., & Mitchell, J. R. (2008) · Pharmacology · doi:10.1159/000136547 · Cited by 1,091 · see citing works
The quest to overcome resistance to EGFR-targeted therapies in cancer
Chong, C. R., & Janne, P. A. (2013) · Nature Medicine · doi:10.1038/nm.3388 · Cited by 1,055 · see citing works
Acetylation of prostaglandin synthase by aspirin.
Roth, G. J., Stanford, N., & Majerus, P. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.8.3073 · Cited by 1,012 · see citing works
The maximal affinity of ligands
Kuntz, I. D., Chen, K., Sharp, K. A., & Kollman, P. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.9997 · Cited by 859 · see citing works
Identification and Biological Activity of the Active Metabolite of Clopidogrel
Savi, P., Pereillo, J., Uzabiaga, M.-F., Combalbert, J., Picard, C., Maffrand, J., Pascal, M., & Herbert, J. (2000) · Thrombosis and Haemostasis · doi:10.1055/s-0037-1614133 · Cited by 752 · see citing works
Stepan, A. F., Walker, D. P., Bauman, J. N., Price, D. A., Baillie, T. A., Kalgutkar, A. S. S., & Aleo, M. D. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200168d · Cited by 711 · 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
Avibactam is a covalent, reversible, non–β-lactam β-lactamase inhibitor
Ehmann, D. E., Jahić, H., Ross, P. L., Gu, R.-F., Hu, J., Kern, G., Walkup, G. K., & Fisher, S. L. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1205073109 · Cited by 548 · see citing works
Proteasome Inhibitors: An Expanding Army Attacking a Unique Target
Kisselev, A. F., van der Linden, W. A., & Overkleeft, H. S. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.01.003 · Cited by 528 · see citing works
Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles
Serafimova, I. M., Pufall, M. A., Krishnan, S., Duda, K., Cohen, M. S., Maglathlin, R. L., McFarland, J. M., Miller, R. M., Frödin, M., & Taunton, J. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.925 · Cited by 496 · see citing works
The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
Gauthier, J. Y., Chauret, N., Cromlish, W. A., Desmarais, S., Duong, L. T., Falgueyret, J., Kimmel, D. B., Lamontagne, S., Léger, S., LeRiche, T., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2007.12.047 · Cited by 479 · see citing works
The Evolving Role of Chemical Synthesis in Antibacterial Drug Discovery
Wright, P. M., Seiple, I. B., & Myers, A. G. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201310843 · Cited by 427 · see citing works
A proton-pump inhibitor expedition: the case histories of omeprazole and esomeprazole
Olbe, L. C., Carlsson, E. I., & Lindberg, P. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1010 · Cited by 419 · see citing works
The clinical development of MEK inhibitors
Zhao, Y., & Adjei, A. A. (2014) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2014.83 · Cited by 403 · see citing works
Biochemical mechanisms of drug action: what does it take for success?
Swinney, D. C. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1500 · Cited by 396 · see citing works
Lammert, C. S., Einarsson, S., Saha, C., Niklasson, A., Bjornsson, E. S., & Chalasani, N. (2008) · Hepatology · doi:10.1002/hep.22272 · Cited by 389 · see citing works
DPP-4 inhibitors and their potential role in the management of type 2 diabetes
Barnett, A. H. (2006) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2006.01178.x · Cited by 389 · see citing works
Strategies for Discovering and Derisking Covalent, Irreversible Enzyme Inhibitors
Johnson, D. S., Weerapana, E., & Cravatt, B. F. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.10.21 · Cited by 387 · see citing works
Development of the Proteasome Inhibitor PS-341
Adams, J. (2002) · The Oncologist · doi:10.1634/theoncologist.7-1-9 · Cited by 376 · see citing works
Covalent Modifiers: An Orthogonal Approach to Drug Design
Potashman, M. H., & Duggan, M. E. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm8008597 · Cited by 348 · see citing works
Vivanco, I., Robins, H. I., Rohle, D., Campos, C., Grommes, C., Nghiemphu, P. L., Kubek, S., Oldrini, B., Chheda, M. G., Yannuzzi, N. A., et al. (2012) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0284 · Cited by 343 · see citing works
Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks
Barf, T., & Kaptein, A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3003203 · Cited by 331 · see citing works
Guerciolini, R. (1997) · PubMed · Cited by 326 · see citing works
Polinsky, R. J. (1998) · Clinical Therapeutics · doi:10.1016/s0149-2918(98)80127-6 · Cited by 323 · see citing works
Role of Metabolism in Drug-Induced Idiosyncratic Hepatotoxicity
Walgren, J. L., Mitchell, M. D., & Thompson, D. C. (2005) · Critical Reviews in Toxicology · doi:10.1080/10408440590935620 · Cited by 320 · see citing works
Ihle, N. T., Williams, R. R., Chow, S., Chew, W. M., Berggren, M. I., Paine-Murrieta, G. D., Minion, D. J., Halter, R. J., Wipf, P., Abraham, R. T., et al. (2004) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.763.3.7 · Cited by 317 · see citing works
Uetrecht, J. (1999) · Chemical Research in Toxicology · doi:10.1021/tx980249i · Cited by 304 · see citing works
Cathepsin K: its skeletal actions and role as a therapeutic target in osteoporosis
Costa, A. G., Cusano, N. E., Silva, B. C. C., Cremers, S., & Bilezikian, J. P. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.77 · Cited by 286 · see citing works
Schwartz, P. A., Kuzmic, P., Solowiej, J., Bergqvist, S., Bolanos, B., Almaden, C., Nagata, A., Ryan, K., Feng, J., Dalvie, D., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1313733111 · Cited by 281 · see citing works
Njoroge, F. G., Chen, K. X., Shih, N., & Piwinski, J. J. (2008) · Accounts of Chemical Research · doi:10.1021/ar700109k · Cited by 269 · see citing works
Structure of the BTB Domain of Keap1 and Its Interaction with the Triterpenoid Antagonist CDDO
Cleasby, A., Yon, J. R., Day, P. J., Richardson, C. J., Tickle, I. J., Williams, P. A., Callahan, J. F., Carr, R. A. E., Concha, N. O., Kerns, J. K., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098896 · Cited by 265 · see citing works
Nakayama, S., Atsumi, R., Takakusa, H., Kobayashi, Y., Kurihara, A., Nagai, Y., Nakai, D., & Okazaki, O. (2009) · Drug Metabolism and Disposition · doi:10.1124/dmd.109.027797 · Cited by 252 · see citing works
Protein‐Reactive Natural Products
DRAHL, C., Cravatt, B. F., & Sorensen, E. J. (2005) · Angewandte Chemie International Edition · doi:10.1002/anie.200500900 · Cited by 251 · see citing works
Mechanistic Basis of Enzyme-Targeted Drugs
Robertson, J. G. (2005) · Biochemistry · doi:10.1021/bi050247e · Cited by 247 · see citing works
Disparate proteome reactivity profiles of carbon electrophiles
Weerapana, E., Simon, G. M., & Cravatt, B. F. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.91 · Cited by 246 · see citing works
Rivastigmine, a New‐Generation Cholinesterase Inhibitor for the Treatment of Alzheimer's Disease
Jann, M. W. (2000) · Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · doi:10.1592/phco.20.1.1.34664 · Cited by 235 · see citing works
Ibrutinib and novel BTK inhibitors in clinical development
Akinleye, A., Chen, Y., Mukhi, N., Song, Y., & Liu, D. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-59 · Cited by 233 · see citing works
Ahn, K., Smith, S. E., Liimatta, M. B., Beidler, D. R., Sadagopan, N., Dudley, D. T., Young, T., Wren, P. B., Zhang, Y., Swaney, S. M., et al. (2011) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.180257 · Cited by 229 · see citing works
Target selection in drug discovery
Knowles, J., & Gromo, G. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd986 · Cited by 216 · see citing works
Active site remodelling accompanies thioester bond formation in the SUMO E1
Olsen, S. K., Capili, A. D., Lu, X., Tan, D. S., & Lima, C. D. (2010) · Nature · doi:10.1038/nature08765 · Cited by 210 · see citing works
Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor
Johnson, D. S., Stiff, C. M., Lazerwith, S. E., Kesten, S. R., Fay, L. K., Morris, M. J., Beidler, D. R., Liimatta, M. B., Smith, S. E., Dudley, D. T., et al. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100190t · Cited by 200 · see citing works
Drug discovery considerations in the development of covalent inhibitors
Mah, R., Thomas, J. R., & Shafer, C. M. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.10.003 · Cited by 197 · see citing works
Electrophilic Fragment-Based Design of Reversible Covalent Kinase Inhibitors
Miller, R. M., Paavilainen, V. O., Krishnan, S., Serafimova, I. M., & Taunton, J. (2013) · Journal of the American Chemical Society · doi:10.1021/ja401221b · Cited by 196 · see citing works
Smith, A. J. T., Zhang, X., Leach, A. G., & Houk, K. N. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm800498e · Cited by 193 · see citing works
Ou, S.-H. I. (2012) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.11.010 · Cited by 182 · see citing works
A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases
Kathman, S. G., Xu, Z., & Statsyuk, A. V. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm500345q · Cited by 172 · see citing works
Keap Calm, and Carry on Covalently
Wilson, A. J., Kerns, J. K., Callahan, J. F., & Moody, C. J. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400224q · Cited by 171 · see citing works
Drug discovery for a new generation of covalent drugs
Kalgutkar, A. S. S., & Dalvie, D. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.688744 · Cited by 169 · see citing works
Jöst, C., Nitsche, C., Scholz, T., Roux, L., & Klein, C. D. P. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm5006918 · Cited by 167 · see citing works
Biomimetic diversity-oriented synthesis of benzannulated medium rings via ring expansion
Bauer, R. A., Wenderski, T. A., & Tan, D. S. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.1130 · Cited by 166 · see citing works
Self-citationEffect of ethacrynic acid on the thick ascending limb of Henle's loop
Burg, M. B., & Green, N. (1973) · Kidney International · doi:10.1038/ki.1973.121 · Cited by 161 · see citing works
Mechanism-Based Inhibition: Deriving KI and kinact Directly from Time-Dependent IC50 Values
Krippendorff, B., Neuhaus, R., Lienau, P., Reichel, A., & Huisinga, W. (2009) · SLAS DISCOVERY · doi:10.1177/1087057109336751 · Cited by 160 · see citing works
Bull, H. G., Garcia-Calvo, M. M., Andersson, S., Baginsky, W. F., Chan, H. K., Ellsworth, D. E., Miller, R. R., Stearns, R. A., Bakshi, R. K., Rasmusson, G. H., et al. (1996) · Journal of the American Chemical Society · doi:10.1021/ja953069t · Cited by 157 · see citing works
Gunnell, D., Murray, V. S. G., & Hawton, K. E. (2000) · Suicide and Life-Threatening Behavior · doi:10.1111/j.1943-278x.2000.tb01098.x · Cited by 128 · see citing works
BIBW-2992, a dual receptor tyrosine kinase inhibitor for the treatment of solid tumors.
Minkovsky, N., & Berezov, A. (2008) · PubMed · Cited by 124 · see citing works
Couch, R. D., Browning, R. G., Honda, T., Gribble, G. W., Wright, D. L., Sporn, M. B., & Anderson, A. C. (2005) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2005.03.031 · Cited by 105 · see citing works
Bruton’s Tyrosine Kinase (BTK) Inhibitors in Clinical Trials
Burger, J. A. (2013) · Current Hematologic Malignancy Reports · doi:10.1007/s11899-013-0188-8 · Cited by 100 · see citing works
Gan, J., Ruan, Q., He, B., Zhu, M., Shyu, W. C., & Humphreys, W. G. (2009) · Chemical Research in Toxicology · doi:10.1021/tx800368n · Cited by 98 · see citing works
Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine
Hagel, M., Niu, D., St Martin, T., Sheets, M. P., Qiao, L., Bernard, H., Karp, R. M., Zhu, Z., Labenski, M. T., Chaturvedi, P., et al. (2011) · Nature Chemical Biology · doi:10.1038/nchembio.492 · Cited by 95 · see citing works
Swinney, D. C. (2006) · Current Topics in Medicinal Chemistry · doi:10.2174/156802606776743093 · Cited by 92 · see citing works
Reversible Michael Additions: Covalent Inhibitors and Prodrugs
Johansson, M. H. (2012) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/13895575112091330 · Cited by 85 · see citing works
Reversible conjugation of ethacrynic acid with glutathione and human glutathione S-transferase P1-1.
Ploemen, J. H. T. M., van Schanke, A., van Ommen, B., & van BLADEREN, P. J. (1994) · PubMed · Cited by 82 · see citing works
Chemical toxicology: reactive intermediates and their role in pharmacology and toxicology
Erve, J. C. L. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.6.923 · Cited by 74 · see citing works
Repeated dose study of sucralose tolerance in human subjects
Baird, I. M., Shephard, N. W., Merritt, R. J., & Hildick‐Smith, G. (2000) · Food and Chemical Toxicology · doi:10.1016/s0278-6915(00)00035-1 · Cited by 72 · see citing works
Hughes, T. E., Kim, D. D., Marjason, J. K., Proietto, J., Whitehead, J. P., & Vath, J. E. (2013) · Obesity · doi:10.1002/oby.20356 · Cited by 67 · see citing works
Inhibition of the methionine aminopeptidase 2 enzyme for the treatment of obesity
Joharapurkar, A. A., Jain, M. R., & Dhanesha, N. (2014) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s56924 · Cited by 55 · see citing works
Shuman, C. F., Markgren, P.-O., Hämäläinen, M., & Danielson, U. H. (2003) · Antiviral Research · doi:10.1016/s0166-3542(03)00002-0 · Cited by 52 · see citing works
MILLER, J. A. (1998) · Drug Metabolism Reviews · doi:10.3109/03602539808996326 · Cited by 51 · see citing works
Koen, Y. M., & Hanzlik, R. P. (2002) · Chemical Research in Toxicology · doi:10.1021/tx0101898 · Cited by 50 · see citing works
US Growth of US manufacturing, global economy will turn up chemical demand
Bomgardner, M. M. (2014) · Chemical & Engineering News · Cited by 49 · see citing works
Kinetic Template‐Guided Tethering of Fragments
Nonoo, R. H., Armstrong, A., & Mann, D. J. (2012) · ChemMedChem · doi:10.1002/cmdc.201200404 · Cited by 47 · see citing works
Sarkar, F. H. (2011) · Springer eBooks · doi:10.1007/978-94-007-2630-7 · Cited by 42 · see citing works
Reversible Covalent Binding of Neratinib to Human Serum Albumin In Vitro
Chandrasekaran, A., Shen, L., Lockhead, S., Oganesian, A., Wang, J., & Scatina, J. (2010) · Drug Metabolism Letters · doi:10.2174/187231210792928206 · Cited by 40 · see citing works
COVALENT DRUGS FORM LONG-LIVED TIES
Guterman, L. (2011) · Chemical & Engineering News · doi:10.1021/cen-v089n036.p019 · Cited by 40 · see citing works
Targeted Covalent Enzyme Inhibitors
Noe, M. C., & Gilbert, A. M. (2012) · Annual reports in medicinal chemistry · doi:10.1016/b978-0-12-396492-2.00027-8 · Cited by 39 · see citing works
Shen, Y., Boivin, R. P., Yoneda, N., Du, H., Schiller, S., Matsushima, T., Goto, M., Shirota, H., Gusovsky, F., Lemelin, C., et al. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.03.087 · Cited by 37 · see citing works
Covalent Adduction of Nitrogen Mustards to Model Protein Nucleophiles
Thompson, V. R., & DeCaprio, A. P. (2013) · Chemical Research in Toxicology · doi:10.1021/tx400188w · Cited by 36 · see citing works
Triptolide binds covalently to a 90 kDa nuclear protein. Role of epoxides in binding and activity
McCallum, C. D., Kwon, S., Leavitt, P. S., Shen, D., Liu, W., & Gurnett, A. M. (2007) · Immunobiology · doi:10.1016/j.imbio.2007.02.002 · Cited by 35 · see citing works
JARVIS, L. M. (2018) · C&EN Global Enterprise · doi:10.1021/cen-09604-cover · Cited by 29 · see citing works
Contact sensitivity to urushiol: Role of covalent bond formation
Dunn, I. S., Liberato, D. J., Castagnoli, N., & Byers, V. S. (1982) · Cellular Immunology · doi:10.1016/0008-8749(82)90023-5 · Cited by 27 · see citing works
Aparo, S., & Goel, S. (2011) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2011.08.006 · Cited by 22 · see citing works
Reversible Michael Additions: Covalent Inhibitors and Prodrugs
Johansson, M. H. (2012) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/138955712804586693 · Cited by 20 · see citing works
A Proposed Screening Paradigm for Discovery of Covalent Inhibitor Drugs
Moghaddam, M. F., Tang, Y., O’Brien, Z., Richardson, S., Bacolod, M. D., Chaturedi, P., Apuy, J. L., & Kulkarni, A. A. (2014) · Drug Metabolism Letters · doi:10.2174/1872312808666140317151735 · Cited by 18 · see citing works
The Pleiotropic Effects of Ethacrynic Acid
Somberg, J. C., & Molnár, J. (2009) · American Journal of Therapeutics · doi:10.1097/mjt.0b013e3181961264 · Cited by 16 · see citing works
Biotech's wellspring: the health of private biotech in 2012
Huggett, B. (2013) · Nature Biotechnology · doi:10.1038/nbt.2577 · Cited by 8 · see citing works
JARVIS, L. M. (2014) · Chemical & Engineering News · doi:10.1021/cen-09204-cover · Cited by 7 · see citing works
Mechanism of Action of the Anti-cancer Agent, Triptolide
Sangwan, V., & Saluja, A. K. (2011) · Springer eBooks · doi:10.1007/978-94-007-2630-7_7 · Cited by 6 · see citing works
Garber, K. (2013) · Nature Biotechnology · doi:10.1038/nbt0513-377 · Cited by 4 · see citing works
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1 of the 97 references couldn’t be matched to a known paper.
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Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity
He, H., Jiang, H., Chen, Y., Ye, J., Wang, A., Wang, C., Liu, Q., Liang, G., Deng, X., Jiang, W., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04947-6 · Cited by 827 · see citing works
Gehringer, M., & Laufer, S. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01153 · Cited by 757 · see citing works
Jackson, P. A., Widen, J. C., Harki, D. A., & Brummond, K. M. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b00788 · Cited by 588 · see citing works
Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease
Douangamath, A., Fearon, D., Gehrtz, P., Krojer, T. J., Lukacik, P., Owen, C. D., Resnick, E., Strain-Damerell, C. M., Aimon, A., Ábrányi‐Balogh, P., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18709-w · Cited by 541 · see citing works
Ertl, P., Altmann, E., & McKenna, J. M. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00754 · Cited by 438 · see citing works
A Perspective on the Kinetics of Covalent and Irreversible Inhibition
Strelow, J. M. (2017) · SLAS Discovery · doi:10.1177/1087057116671509 · Cited by 392 · see citing works
Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works
Covalent inhibitors: a rational approach to drug discovery
Sutanto, F., Konstantinidou, M., & Dömling, A. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00154f · Cited by 389 · see citing works
Guo, Y., Liu, Y., Hu, N., Yu, D., Zhou, C., Shi, G., Zhang, B., Wei, M., Liu, J., Luo, L., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00687 · Cited by 372 · see citing works
Redox Signaling by Reactive Electrophiles and Oxidants
Parvez, S., Long, M. J. C., Poganik, J. R., & Aye, Y. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00698 · Cited by 357 · see citing works
Advances in covalent kinase inhibitors
Abdeldayem, A., Raouf, Y. S., Constantinescu, S. N., Moriggl, R., & Gunning, P. T. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00720b · Cited by 332 · see citing works
Rapid Covalent-Probe Discovery by Electrophile-Fragment Screening
Resnick, E., Bradley, A., Gan, J., Douangamath, A., Krojer, T., Sethi, R., Geurink, P. P., Aimon, A., Amitai, G., Bellini, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b02822 · Cited by 335 · see citing works
Covalent inhibitors design and discovery.
De Cesco, S., Kurian, J., Dufresne, C., Mittermaier, A. K., & Moitessier, N. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.06.019 · Cited by 315 · see citing works
Mortenson, D. E., Brighty, G. J., Plate, L., Bare, G. A. L., Chen, W., Li, S., Wang, H., Cravatt, B. F., Forli, S., Powers, E. T., et al. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b08366 · Cited by 301 · see citing works
Next generation 3D pharmacophore modeling
Schaller, D., Šribar, D., Noonan, T., Deng, L., Nguyen, T. N., Pach, S., Machalz, D., Bermúdez, M., & Wolber, G. (2020) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1468 · Cited by 276 · see citing works
Covalent Inhibition in Drug Discovery
Ghosh, A. K., Samanta, I., Mondal, A., & Liu, W. R. (2019) · ChemMedChem · doi:10.1002/cmdc.201900107 · Cited by 265 · see citing works
Pike, A., Williamson, B., Harlfinger, S., Martin, S. W., & McGinnity, D. F. (2020) · Drug Discovery Today · doi:10.1016/j.drudis.2020.07.013 · Cited by 247 · see citing works
Lysine‐Targeting Covalent Inhibitors
Pettinger, J., Jones, K., & Cheeseman, M. D. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201707630 · Cited by 244 · see citing works
Liu, X. R., Zhang, M. M., & Gross, M. L. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00815 · Cited by 241 · see citing works
Mechanistic enzymology in drug discovery: a fresh perspective
Holdgate, G. A., Meek, T. D., & Grimley, R. L. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.219 · Cited by 224 · see citing works
Developing Covalent Protein Drugs via Proximity-Enabled Reactive Therapeutics
Li, Q., Qu, C., Klauser, P. C., Li, M., Zheng, F. J., Wang, N., Li, X., Zhang, Q., Fu, X., Wang, Q., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.028 · Cited by 214 · see citing works
Bruton tyrosine kinase inhibitors for multiple sclerosis
Krämer, J., Bar-Or, A., Turner, T. J., & Wiendl, H. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00800-7 · Cited by 206 · see citing works
Su, H., Yao, S., Zhao, W., Zhang, Y., Liu, J., Shao, Q., Wang, Q., Li, M., Xie, H., Shang, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23751-3 · Cited by 199 · see citing works
The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors
Zhan, X., Li, Q., Xu, G., Xiao, X., & Bai, Z. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1109938 · Cited by 191 · see citing works
Expanding the Armory: Predicting and Tuning Covalent Warhead Reactivity
Lonsdale, R., Burgess, J., Colclough, N., Davies, N. L., Lenz, E. M., Orton, A. L., & Ward, R. A. (2017) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.7b00553 · Cited by 190 · see citing works
Overview of Recent Strategic Advances in Medicinal Chemistry
Wu, G., Zhao, T., Kang, D., Zhang, J., Song, Y., Namasivayam, V., Kongsted, J., Pannecouque, C. C., Clercq, E. D., Poongavanam, V., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00359 · Cited by 183 · see citing works
Targeting MIF in Cancer: Therapeutic Strategies, Current Developments, and Future Opportunities
O’Reilly, C., Doroudian, M., Mawhinney, L., & Donnelly, S. C. (2016) · Medicinal Research Reviews · doi:10.1002/med.21385 · Cited by 182 · see citing works
Erratum: Mechanistic enzymology in drug discovery: a fresh perspective
Holdgate, G. A., Meek, T. D., & Grimley, R. L. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.257 · Cited by 182 · see citing works
The Symbiotic Relationship Between Drug Discovery and Organic Chemistry
Grygorenko, O. O., Volochnyuk, D. M., Ryabukhin, S. V., & Judd, D. B. (2019) · Chemistry - A European Journal · doi:10.1002/chem.201903232 · Cited by 172 · see citing works
De Novo Design at the Edge of Chaos
Schneider, P., & Schneider, G. (2016) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01849 · Cited by 167 · see citing works
Cee, V. J., Volak, L. P., Chen, Y., Bartberger, M. D., Tegley, C. M., Arvedson, T., McCarter, J. D., Tasker, A. S., & Fotsch, C. H. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01018 · Cited by 164 · see citing works
The Taxonomy of Covalent Inhibitors
Tuley, A., & Fast, W. L. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00315 · Cited by 163 · see citing works
ERK1/2 inhibitors: New weapons to inhibit the RAS-regulated RAF-MEK1/2-ERK1/2 pathway
Kidger, A. M., Sipthorp, J., & Cook, S. J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.02.007 · Cited by 161 · see citing works
Cisar, J. S., Weber, O. D., Clapper, J. R., Blankman, J. L., Henry, C. L., Simon, G. M., Alexander, J. P., Jones, T. K., Ezekowitz, R. A. B., O’Neill, G. P., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00951 · Cited by 161 · see citing works
Liu, Y., Guo, Q., Yang, H., Zhang, X., Feng, N., Wang, J.-K., Liu, T., Zeng, K., & Tu, P. (2022) · ACS Central Science · doi:10.1021/acscentsci.2c00107 · Cited by 160 · see citing works
Krenske, E. H., Petter, R. C., & Houk, K. N. (2016) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.6b02188 · Cited by 152 · see citing works
Comparative Evaluation of Covalent Docking Tools
Scarpino, A., Ferenczy, G. G., & Keserű, G. M. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00228 · Cited by 152 · see citing works
Zhang, X., Xu, A., Lv, J., Zhang, Q., Ran, Y., Wei, C., & Wu, J. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111822 · Cited by 147 · see citing works
A Survey of the Role of Nitrile Groups in Protein–Ligand Interactions
Wang, Y. E., Du, Y., & Huang, N. (2018) · Future Medicinal Chemistry · doi:10.4155/fmc-2018-0252 · Cited by 142 · see citing works
Brighty, G. J., Botham, R. C., Li, S., Nelson, L. T., Mortenson, D. E., Li, G., Morisseau, C. H. P., Wang, H., Hammock, B. D., Sharpless, K. B., et al. (2020) · Nature Chemistry · doi:10.1038/s41557-020-0530-4 · Cited by 144 · see citing works
Arafet, K., Serrano-Aparicio, N., Lodola, A., Mulholland, A. J., González, F. V., Świderek, K., & Moliner, V. (2020) · Chemical Science · doi:10.1039/d0sc06195f · Cited by 138 · see citing works
Hatcher, J. M., Wu, G., Zeng, C., Zhu, J., Fan, M., Patel, S. H., Wang, W., Ficarro, S. B., Leggett, A. L., Powell, C. E., et al. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.01.013 · Cited by 133 · see citing works
A road map for prioritizing warheads for cysteine targeting covalent inhibitors
Ábrányi‐Balogh, P., Petri, L., Imre, T., Szijj, P. A., Scarpino, A., Hrast, M., Mitrović, A., Fonović, U. P., Németh, K., Barreteau, H., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.010 · Cited by 132 · see citing works
Glycomimetics for the inhibition and modulation of lectins
Leusmann, S., Ménová, P., Shanina, E., Titz, A., & Rademacher, C. (2023) · Chemical Society Reviews · doi:10.1039/d2cs00954d · Cited by 135 · see citing works
Diacylfuroxans Are Masked Nitrile Oxides That Inhibit GPX4 Covalently
Eaton, J. K., Ruberto, R. A., Kramm, A., Viswanathan, V. S., & Schreiber, S. L. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b10769 · Cited by 130 · see citing works
10 Years Into the Resurgence of Covalent Drugs
Vita, E. D. (2020) · Future Medicinal Chemistry · doi:10.4155/fmc-2020-0236 · Cited by 125 · see citing works
Fairhurst, R. A., Knöpfel, T. F., Buschmann, N., Leblanc, C., Mah, R., Todorov, M., Nimsgern, P., Ripoche, S., Niklaus, M., Warin, N., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01019 · Cited by 127 · see citing works
Recent developments with rhodanine as a scaffold for drug discovery
Kaminskyy, D. V., Kryshchyshyn‐Dylevych, A., & Lesyk, R. (2017) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1388370 · Cited by 122 · see citing works
Mons, E., Roet, S., Kim, R. Q., & Mulder, M. P. C. (2022) · Current Protocols · doi:10.1002/cpz1.419 · Cited by 123 · see citing works
Mons, E., Jansen, I., Loboda, J., van Doodewaerd, B. R., Hermans, J., Verdoes, M., Boeckel, C. V. V., van Veelen, P. V., Turk, B., Turk, D., et al. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.8b11027 · Cited by 96 · see citing works
Covalent Warheads Targeting Cysteine Residue: The Promising Approach in Drug Development
Huang, F., Han, X., Xiao, X., & Zhou, J. (2022) · Molecules · doi:10.3390/molecules27227728 · Cited by 123 · see citing works
Recent advances in the development of covalent inhibitors
Kim, H., Hwang, Y. S., Kim, M., & Park, S. B. (2021) · RSC Medicinal Chemistry · doi:10.1039/d1md00068c · Cited by 114 · see citing works
Ebselen, a Small-Molecule Capsid Inhibitor of HIV-1 Replication
Thenin-Houssier, S., de Vera, I. M. S., Pedró-Rosa, L., Brady, A., Richard, A. S., Konnick, B., Opp, S., Buffone, C., Fuhrmann, J., Kota, S., et al. (2016) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02574-15 · Cited by 114 · see citing works
Quan, B., Shuai, H., Xia, A., Hou, Y., Zeng, R., Liu, X., Lin, G., Qiao, J., Li, W.-P., Wang, F., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01119-7 · Cited by 114 · see citing works
New Electrophiles and Strategies for Mechanism-Based and Targeted Covalent Inhibitor Design
Ray, S., & Murkin, A. S. (2019) · Biochemistry · doi:10.1021/acs.biochem.9b00293 · Cited by 108 · see citing works
Progress in the Development of Small Molecular Inhibitors of Focal Adhesion Kinase (FAK)
Lu, Y., & Sun, H. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01248 · Cited by 104 · see citing works
Macip, G., Garcia‐Segura, P., Mestres‐Truyol, J., Saldivar‐Espinoza, B., Ojeda, M. J., Gimeno, A., Cereto‐Massagué, A., Garcı́a-Vallvé, S., & Pujadas, G. (2021) · Medicinal Research Reviews · doi:10.1002/med.21862 · Cited by 105 · see citing works
Recent Advances in Covalent Drug Discovery
Schaefer, D., & Cheng, X. (2023) · Pharmaceuticals · doi:10.3390/ph16050663 · Cited by 106 · see citing works
Advanced Activity-Based Protein Profiling Application Strategies for Drug Development
Wang, S., Tian, Y., Wang, M., Wang, M., Sun, G., & Sun, X. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00353 · Cited by 101 · see citing works
Strategies for targeting undruggable targets
Zhang, G., Zhang, J., Gao, Y., Li, Y., & Li, Y. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1969359 · Cited by 102 · see citing works
Covalent Small Molecules as Enabling Platforms for Drug Discovery
Dalton, S. E., & Campos, S. (2019) · ChemBioChem · doi:10.1002/cbic.201900674 · Cited by 98 · see citing works
Targeting the RdRp of Emerging RNA Viruses: The Structure-Based Drug Design Challenge
Picarazzi, F., Vicenti, I., Saladini, F., Zazzi, M., & Mori, M. (2020) · Molecules · doi:10.3390/molecules25235695 · Cited by 94 · see citing works
Beyond cysteine: recent developments in the area of targeted covalent inhibition
Mukherjee, H., & Grimster, N. P. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.011 · Cited by 95 · see citing works
Covalent targeting of acquired cysteines in cancer
Visscher, M., Arkin, M. R., & Dansen, T. B. (2016) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2015.11.004 · Cited by 95 · see citing works
Drug Design Strategies to Avoid Resistance in Direct-Acting Antivirals and Beyond
Matthew, A. N., Leidner, F., Lockbaum, G. J., Henes, M., Zephyr, J., Hou, S., Rao, D. N., Timm, J., Rusere, L. N., Ragland, D. A., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00648 · Cited by 93 · see citing works
Nitro-fatty acids: New drug candidates for chronic inflammatory and fibrotic diseases
Schopfer, F. J., Vitturi, D. A., Jorkasky, D. K., & Freeman, B. Α. (2018) · Nitric Oxide · doi:10.1016/j.niox.2018.06.006 · Cited by 91 · see citing works
A Chemoproteomic Strategy for Direct and Proteome-Wide Covalent Inhibitor Target-Site Identification
Browne, C. M., Jiang, B., Ficarro, S. B., Doctor, Z. M., Johnson, J. L., Card, J. D., Sivakumaren, S. C., Alexander, W. M., Yaron, T. M., Murphy, C. J., et al. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b07911 · Cited by 90 · see citing works
Modeling covalent-modifier drugs.
Awoonor-Williams, E., Walsh, A. G., & Rowley, C. N. (2017) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2017.05.009 · Cited by 90 · see citing works
Can Cysteine Protease Cross-class Inhibitors Achieve Selectivity?
Cianni, L., Feldmann, C., Gilberg, E., Gütschow, M., Juliano, L., Leitão, A., Bajorath, J., & Montanari, C. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b00683 · Cited by 65 · see citing works
McAulay, K., Hoyt, E. A., Thomas, M. C., Schimpl, M., Bodnarchuk, M. S., Lewis, H. J., Barratt, D. G., Bhavsar, D., Robinson, D. M., Deery, M. J., et al. (2020) · Journal of the American Chemical Society · doi:10.1021/jacs.9b13391 · Cited by 85 · see citing works
Strategic Design of Catalytic Lysine‐Targeting Reversible Covalent BCR‐ABL Inhibitors**
Quach, D., Tang, G., Anantharajan, J., Baburajendran, N., Poulsen, A., Wee, J. L. K., Retna, P., Li, R., Liu, B., Tee, D. H. Y., et al. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202105383 · Cited by 83 · see citing works
Machine learning activation energies of chemical reactions
Lewis‐Atwell, T., Townsend, P. A., & Grayson, M. N. (2021) · Wiley Interdisciplinary Reviews Computational Molecular Science · doi:10.1002/wcms.1593 · Cited by 85 · see citing works
Privileged Electrophile Sensors: A Resource for Covalent Drug Development
Long, M. J. C., & Aye, Y. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.05.023 · Cited by 81 · see citing works
Drug-Target Residence Time Affects in Vivo Target Occupancy through Multiple Pathways
Lee, K. S. S., Yang, J., Niu, J., Ng, C., Wagner, K. M., Dong, H., Kodani, S. D., Wan, D., Morisseau, C. H. P., & Hammock, B. D. (2019) · ACS Central Science · doi:10.1021/acscentsci.9b00770 · Cited by 81 · see citing works
Design, Synthesis, and Evaluation of Acrylamide Derivatives as Direct NLRP3 Inflammasome Inhibitors
Cocco, M., Miglio, G., Giorgis, M., Garella, D., Marini, E., Costale, A., Regazzoni, L., Vistoli, G., Orioli, M., Massulaha‐Ahmed, R., et al. (2016) · ChemMedChem · doi:10.1002/cmdc.201600055 · Cited by 80 · see citing works
Aljoundi, A., Bjij, I., El-Rashedy, A. A. E., & Soliman, M. E. S. (2020) · The Protein Journal · doi:10.1007/s10930-020-09884-2 · Cited by 78 · see citing works
Inhibitors of the ATPase p97/VCP: From basic research to clinical applications
Kilgas, S., & Ramadan, K. (2023) · Cell chemical biology · doi:10.1016/j.chembiol.2022.12.007 · Cited by 78 · see citing works
Designing Irreversible Inhibitors—Worth the Effort?
González‐Bello, C. (2016) · ChemMedChem · doi:10.1002/cmdc.201500469 · Cited by 74 · see citing works
Birkholz, A. B., Kopecky, D. J., Volak, L. P., Bartberger, M. D., Chen, Y., Tegley, C. M., Arvedson, T., McCarter, J. D., Fotsch, C. H., & Cee, V. J. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00749 · Cited by 74 · see citing works
Drugging K-RasG12C through covalent inhibitors: Mission possible?
Ni, D., Li, X., He, X., Zhang, H., Zhang, J., & Lu, S. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.06.007 · Cited by 73 · see citing works
Thorarensen, A., Balbo, P., Banker, M. E., Czerwiński, R., Kühn, M., Maurer, T. S., Telliez, J., Vincent, F., & Wittwer, A. J. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115865 · Cited by 72 · see citing works
Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery
Hallenbeck, K. K., Turner, D., Renslo, A. R., & Arkin, M. R. (2016) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026616666160719163839 · Cited by 71 · see citing works
Development of covalent inhibitors: Principle, design, and application in cancer
Zheng, L., Li, Y., Wu, D., Xiao, H., Zheng, S., Wang, G., & Sun, Q. (2023) · MedComm – Oncology · doi:10.1002/mog2.56 · Cited by 71 · see citing works
Milik, S. N., Lasheen, D. S., Serya, R. A. T., & Abouzid, K. A. M. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.07.023 · Cited by 71 · see citing works
Discovery of Potent and Selective Covalent Protein Arginine Methyltransferase 5 (PRMT5) Inhibitors
Lin, H., Wang, M., Zhang, Y. W., Tong, S., Leal, R., Shetty, R. S., Vaddi, K., & Luengo, J. I. (2019) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.9b00074 · Cited by 69 · see citing works
Baggio, C., Udompholkul, P., Gambini, L., Salem, A. F., Jossart, J. N., Perry, J. J. P., & Pellecchia, M. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01108 · Cited by 66 · see citing works
Applications of covalent chemistry in targeted protein degradation
Lu, D., Yu, X., Lin, H., Cheng, R., Monroy, E. Y., Qi, X., Wang, M. C., & Wang, J. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00362g · Cited by 66 · see citing works
Covalent inhibition of protein tyrosine phosphatases
Ruddraraju, K. V., & Zhang, Z. (2017) · Molecular BioSystems · doi:10.1039/c7mb00151g · Cited by 62 · see citing works
Khoo, N. K. H., Li, L., Salvatore, S. R., Schopfer, F. J., & Freeman, B. Α. (2018) · Scientific Reports · doi:10.1038/s41598-018-20460-8 · Cited by 63 · see citing works
Docking of Covalent Ligands: Challenges and Approaches
Sotriffer, C. (2018) · Molecular Informatics · doi:10.1002/minf.201800062 · Cited by 61 · see citing works
Positive Allosteric Modulation of the Glucagon-like Peptide-1 Receptor by Diverse Electrophiles
Bueno, A. B., Showalter, A. D., Wainscott, D. B., Stutsman, C., Marín, A., FICORILLI, J. V., Cabrera, O., Willard, F. S., & Sloop, K. W. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.696039 · Cited by 60 · see citing works
Kinetic Optimization of Lysine-Targeting Covalent Inhibitors of HSP72
Pettinger, J., Carter, M., Jones, K., & Cheeseman, M. D. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01709 · Cited by 59 · see citing works
Covalent peptides and proteins for therapeutics
Berdan, V. Y., Klauser, P. C., & Wang, L. (2020) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2020.115896 · Cited by 59 · see citing works
McCune, C. D., Beio, M. L., Sturdivant, J. M., de la Salud‐Bea, R., Darnell, B. M., & Berkowitz, D. B. (2017) · Journal of the American Chemical Society · doi:10.1021/jacs.7b04690 · Cited by 57 · see citing works
The Proteome‐Wide Potential for Reversible Covalency at Cysteine
Senkane, K., Vinogradova, E. V., Suciu, R. M., Crowley, V. M., Zaro, B. W., Bradshaw, J. M., Brameld, K. A., & Cravatt, B. F. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201905829 · Cited by 57 · see citing works
Xie, F., Zhang, H., Zheng, C., & Shen, X. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106567 · Cited by 57 · see citing works
How Reactive are Druggable Cysteines in Protein Kinases?
Awoonor‐Williams, E., & Rowley, C. N. (2018) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.8b00454 · Cited by 57 · see citing works
Kharenko, O. A., Patel, R. G., Brown, S. D., Calosing, C., White, A., Damodharan, L., Suto, R. K., Duffy, B. C., Kitchen, D. B., McLure, K. G., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00666 · Cited by 56 · see citing works
Drug design targeting active posttranslational modification protein isoforms
Meng, F., Liang, Z. T., Zhao, K., & Luo, C. (2020) · Medicinal Research Reviews · doi:10.1002/med.21774 · Cited by 56 · see citing works
- Authors
- Bauer, R. A.
- Affiliations
- Eli Lilly (United States) (US)
- Corresponding author
- Bauer, Renato A.
- ORCID
- Bauer, Renato A.
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 20
- Issue
- 9
- Pages
- 1061-1073
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W248383993
- Cited by
- 534
- References
- 97
- Citations by year
- 2026: 36 · 2025: 43 · 2024: 46 · 2023: 56 · 2022: 57 · 2021: 70 · 2020: 57 · 2019: 51 · 2018: 47 · 2017: 33 · 2016: 29 · 2015: 8
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- covalent inhibitors, covalent drug design, history of drug discovery, drug toxicity, drug resistance, oncology therapeutics, infectious disease therapeutics, therapeutic window
- MeSH terms
- Drug Resistance, Pharmaceutical Preparations, Humans, Pharmacokinetics, Drug Design, Drug Approval, Drug Discovery, Molecular Targeted Therapy
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.
What counts as a claim ›How we measure confidence ›How we check this ›
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