Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Mini-Review Article

Fragment-based Drug Discovery Successful Contributions to Current Pharmacotherapeutic Agents Arsenal against Aggressive Cancers: A Mini-Review

Author(s): Leandro Marcos Santos* and Nelson José Freitas da Silveira

Volume 23, Issue 16, 2023

Published on: 31 July, 2023

Page: [1796 - 1810] Pages: 15

DOI: 10.2174/1871520623666230714163823

Price: $65

Abstract

After a decade of approval of the drug vemurafenib in 2011, the hopeless scenario imposed by some severe cancer types has been mitigated by the magic bullets developed through fragment-based drug discovery. Moreover, this recent approach to medicinal chemistry has been successfully practiced by academic laboratories and pharmaceutical industry workflows focused on drug design with an enhanced profile for chemotherapy of aggressive tumors. This mini-review highlights the successes achieved by these research campaigns in the fruitful field of the molecular fragment paradigm that resulted in the approval of six new anticancer drugs in the last decade (2011-2021), as well as several promising clinical candidates. It is a particularly encouraging opportunity for other researchers who want to become aware of the applicability and potency of this new paradigm applied to the design and development of powerful molecular weapons in the constant war against these merciless scourges of humanity.

« Previous Next »
Graphical Abstract

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Ugai, T.; Sasamoto, N.; Lee, H.Y.; Ando, M.; Song, M.; Tamimi, R.M.; Kawachi, I.; Campbell, P.T.; Giovannucci, E.L.; Weiderpass, E.; Rebbeck, T.R.; Ogino, S. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat. Rev. Clin. Oncol., 2022, 19(10), 656-673.
[http://dx.doi.org/10.1038/s41571-022-00672-8] [PMID: 36068272]
[3]
Chen, W.; Sun, Z.; Lu, L. Targeted engineering of medicinal chemistry for cancer therapy: Recent advances and perspectives. Angew. Chem. Int. Ed., 2021, 60(11), 5626-5643.
[http://dx.doi.org/10.1002/anie.201914511] [PMID: 32096328]
[4]
Stine, Z.E.; Schug, Z.T.; Salvino, J.M.; Dang, C.V. Targeting cancer metabolism in the era of precision oncology. Nat. Rev. Drug Discov., 2022, 21(2), 141-162.
[http://dx.doi.org/10.1038/s41573-021-00339-6] [PMID: 34862480]
[5]
Pedreira, J.G.B.; Franco, L.S.; Barreiro, E.J. Chemical intuition in drug design and discovery. Curr. Top. Med. Chem., 2019, 19(19), 1679-1693.
[http://dx.doi.org/10.2174/1568026619666190620144142] [PMID: 31258088]
[6]
Fischer, E. Einfluss der configuration auf die wirkung der enzima. Ber. Dtsch. Chem. Ges., 1894, 27(3), 2985-2993.
[http://dx.doi.org/10.1002/cber.18940270364]
[7]
Ehrlich, P. Chemotherapeutics: Scientific principles, methods and results. Lancet, 1913, 182, 445-451.
[http://dx.doi.org/10.1016/S0140-6736(01)38705-6]
[8]
Li, Q.; Kang, C. Perspectives on fragment-based drug discovery: A strategy applicable to diverse targets. Curr. Top. Med. Chem., 2021, 21(13), 1099-1112.
[http://dx.doi.org/10.2174/1568026621666210804115700] [PMID: 34348623]
[9]
Bon, M.; Bilsland, A.; Bower, J.; McAulay, K. Fragment‐based drug discovery—the importance of high‐quality molecule libraries. Mol. Oncol., 2022, 16(21), 3761-3777.
[http://dx.doi.org/10.1002/1878-0261.13277] [PMID: 35749608]
[10]
de Esch, I.J.P.; Erlanson, D.A.; Jahnke, W.; Johnson, C.N.; Walsh, L. Fragment-to-lead medicinal chemistry publications in 2020. J. Med. Chem., 2022, 65(1), 84-99.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01803] [PMID: 34928151]
[11]
Erlanson, D. Practical fragments. Available From: https://practicalfragments.blogspot.com/2022/11/fragments-in-clinic-2022-edition.html (accessed December 20, 2022).
[12]
Rapp, U.R.; Goldsborough, M.D.; Mark, G.E.; Bonner, T.I.; Groffen, J.; Reynolds, F.H., Jr; Stephenson, J.R. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc. Natl. Acad. Sci. USA, 1983, 80(14), 4218-4222.https://www.pnas.org/doi/pdf/10.1073/pnas.80.14.4218
[http://dx.doi.org/10.1073/pnas.80.14.4218] [PMID: 6308607]
[13]
Beck, T.W.; Huleihel, M.; Gunnell, M.; Bonner, T.I.; Rapp, U.R. The complete coding sequence of the human A- raf -1 oncogene and transforming activity of a human A- raf carrying retrovirus. Nucleic Acids Res., 1987, 15(2), 595-609.
[http://dx.doi.org/10.1093/nar/15.2.595] [PMID: 3029685]
[14]
Ikawa, S.; Fukui, M.; Ueyama, Y.; Tamaoki, N.; Yamamoto, T.; Toyoshima, K. B-raf, a new member of the raf family, is activated by DNA rearrangement. Mol. Cell. Biol., 1988, 8(6), 2651-2654.
[http://dx.doi.org/10.1128/mcb.8.6.2651-2654.1988] [PMID: 3043188]
[15]
Holderfield, M.; Deuker, M.M.; McCormick, F.; McMahon, M. Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond. Nat. Rev. Cancer, 2014, 14(7), 455-467.
[http://dx.doi.org/10.1038/nrc3760] [PMID: 24957944]
[16]
Davies, H.; Bignell, G.R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M.J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B.A.; Cooper, C.; Shipley, J.; Hargrave, D.; Pritchard-Jones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G.J.; Bigner, D.D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J.W.C.; Leung, S.Y.; Yuen, S.T.; Weber, B.L.; Seigler, H.F.; Darrow, T.L.; Paterson, H.; Marais, R.; Marshall, C.J.; Wooster, R.; Stratton, M.R.; Futreal, P.A. Mutations of the BRAF gene in human cancer. Nature, 2002, 417(6892), 949-954.
[http://dx.doi.org/10.1038/nature00766] [PMID: 12068308]
[17]
Schirripa, M.; Biason, P.; Lonardi, S.; Pella, N.; Pino, M.S.; Urbano, F.; Antoniotti, C.; Cremolini, C.; Corallo, S.; Pietrantonio, F.; Gelsomino, F.; Cascinu, S.; Orlandi, A.; Munari, G.; Malapelle, U.; Saggio, S.; Fontanini, G.; Rugge, M.; Mescoli, C.; Lazzi, S.; Reggiani Bonetti, L.; Lanza, G.; Dei Tos, A.P.; De Maglio, G.; Martini, M.; Bergamo, F.; Zagonel, V.; Loupakis, F.; Fassan, M. Class 1, 2, and 3 BRAF-mutated metastatic colorectal cancer: A detailed clinical, pathologic, and molecular characterization. Clin. Cancer Res., 2019, 25(13), 3954-3961.
[http://dx.doi.org/10.1158/1078-0432.CCR-19-0311] [PMID: 30967421]
[18]
Śmiech, M.; Leszczyński, P.; Kono, H.; Wardell, C.; Taniguchi, H. Emerging BRAF mutations in cancer progression and their possible effects on transcriptional networks. Genes, 2020, 11(11), 1342.
[http://dx.doi.org/10.3390/genes11111342] [PMID: 33198372]
[19]
Ko, J.S. The immunology of melanoma. Clin. Lab. Med., 2017, 37(3), 449-471.
[http://dx.doi.org/10.1016/j.cll.2017.06.001] [PMID: 28802495]
[20]
Kumar, A.; Mandiyan, V.; Suzuki, Y.; Zhang, C.; Rice, J.; Tsai, J.; Artis, D.R.; Ibrahim, P.; Bremer, R. Crystal structures of proto-oncogene kinase Pim1: A target of aberrant somatic hypermutations in diffuse large cell lymphoma. J. Mol. Biol., 2005, 348(1), 183-193.
[http://dx.doi.org/10.1016/j.jmb.2005.02.039] [PMID: 15808862]
[21]
Tsai, J.; Lee, J.T.; Wang, W.; Zhang, J.; Cho, H.; Mamo, S.; Bremer, R.; Gillette, S.; Kong, J.; Haass, N.K.; Sproesser, K.; Li, L.; Smalley, K.S.M.; Fong, D.; Zhu, Y.L.; Marimuthu, A.; Nguyen, H.; Lam, B.; Liu, J.; Cheung, I.; Rice, J.; Suzuki, Y.; Luu, C.; Settachatgul, C.; Shellooe, R.; Cantwell, J.; Kim, S.H.; Schlessinger, J.; Zhang, K.Y.J.; West, B.L.; Powell, B.; Habets, G.; Zhang, C.; Ibrahim, P.N.; Hirth, P.; Artis, D.R.; Herlyn, M.; Bollag, G. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl. Acad. Sci. USA, 2008, 105(8), 3041-3046.
[http://dx.doi.org/10.1073/pnas.0711741105] [PMID: 18287029]
[22]
Bollag, G.; Hirth, P.; Tsai, J.; Zhang, J.; Ibrahim, P.N.; Cho, H.; Spevak, W.; Zhang, C.; Zhang, Y.; Habets, G.; Burton, E.A.; Wong, B.; Tsang, G.; West, B.L.; Powell, B.; Shellooe, R.; Marimuthu, A.; Nguyen, H.; Zhang, K.Y.J.; Artis, D.R.; Schlessinger, J.; Su, F.; Higgins, B.; Iyer, R.; D’Andrea, K.; Koehler, A.; Stumm, M.; Lin, P.S.; Lee, R.J.; Grippo, J.; Puzanov, I.; Kim, K.B.; Ribas, A.; McArthur, G.A.; Sosman, J.A.; Chapman, P.B.; Flaherty, K.T.; Xu, X.; Nathanson, K.L.; Nolop, K. Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature, 2010, 467(7315), 596-599.
[http://dx.doi.org/10.1038/nature09454] [PMID: 20823850]
[23]
Flaherty, K.T.; Yasothan, U.; Kirkpatrick, P. Vemurafenib. Nat. Rev. Drug Discov., 2011, 10(11), 811-812.
[http://dx.doi.org/10.1038/nrd3579] [PMID: 22037033]
[24]
Bollag, G.; Tsai, J.; Zhang, J.; Zhang, C.; Ibrahim, P.; Nolop, K.; Hirth, P. Vemurafenib: The first drug approved for BRAF-mutant cancer. Nat. Rev. Drug Discov., 2012, 11(11), 873-886.
[http://dx.doi.org/10.1038/nrd3847] [PMID: 23060265]
[25]
Brown, D.G.; Wobst, H.J. A decade of FDA-approved drugs (2010-2019): Trends and future directions. J. Med. Chem., 2021, 64(5), 2312-2338.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01516] [PMID: 33617254]
[26]
Muchmore, S.W.; Sattler, M.; Liang, H.; Meadows, R.P.; Harlan, J.E.; Yoon, H.S.; Nettesheim, D.; Chang, B.S.; Thompson, C.B.; Wong, S.L.; Ng, S.C.; Fesik, S.W. X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death. Nature, 1996, 381(6580), 335-341.
[http://dx.doi.org/10.1038/381335a0] [PMID: 8692274]
[27]
Oltersdorf, T.; Elmore, S.W.; Shoemaker, A.R.; Armstrong, R.C.; Augeri, D.J.; Belli, B.A.; Bruncko, M.; Deckwerth, T.L.; Dinges, J.; Hajduk, P.J.; Joseph, M.K.; Kitada, S.; Korsmeyer, S.J.; Kunzer, A.R.; Letai, A.; Li, C.; Mitten, M.J.; Nettesheim, D.G.; Ng, S.; Nimmer, P.M.; O’Connor, J.M.; Oleksijew, A.; Petros, A.M.; Reed, J.C.; Shen, W.; Tahir, S.K.; Thompson, C.B.; Tomaselli, K.J.; Wang, B.; Wendt, M.D.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature, 2005, 435(7042), 677-681.
[http://dx.doi.org/10.1038/nature03579] [PMID: 15902208]
[28]
Shoemaker, A.R.; Oleksijew, A.; Bauch, J.; Belli, B.A.; Borre, T.; Bruncko, M.; Deckwirth, T.; Frost, D.J.; Jarvis, K.; Joseph, M.K.; Marsh, K.; McClellan, W.; Nellans, H.; Ng, S.; Nimmer, P.; O’Connor, J.M.; Oltersdorf, T.; Qing, W.; Shen, W.; Stavropoulos, J.; Tahir, S.K.; Wang, B.; Warner, R.; Zhang, H.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W. A small-molecule inhibitor of Bcl-XL potentiates the activity of cytotoxic drugs in vitro and in vivo. Cancer Res., 2006, 66(17), 8731-8739.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0367] [PMID: 16951189]
[29]
Tse, C.; Shoemaker, A.R.; Adickes, J.; Anderson, M.G.; Chen, J.; Jin, S.; Johnson, E.F.; Marsh, K.C.; Mitten, M.J.; Nimmer, P.; Roberts, L.; Tahir, S.K.; Xiao, Y.; Yang, X.; Zhang, H.; Fesik, S.; Rosenberg, S.H.; Elmore, S.W. ABT-263: A potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res., 2008, 68(9), 3421-3428.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5836] [PMID: 18451170]
[30]
Ackler, S.; Xiao, Y.; Mitten, M.J.; Foster, K.; Oleksijew, A.; Refici, M.; Schlessinger, S.; Wang, B.; Chemburkar, S.R.; Bauch, J.; Tse, C.; Frost, D.J.; Fesik, S.W.; Rosenberg, S.H.; Elmore, S.W.; Shoemaker, A.R. ABT-263 and rapamycin act cooperatively to kill lymphoma cells in vitro and in vivo. Mol. Cancer Ther., 2008, 7(10), 3265-3274.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0268] [PMID: 18852130]
[31]
Souers, A.J.; Leverson, J.D.; Boghaert, E.R.; Ackler, S.L.; Catron, N.D.; Chen, J.; Dayton, B.D.; Ding, H.; Enschede, S.H.; Fairbrother, W.J.; Huang, D.C.S.; Hymowitz, S.G.; Jin, S.; Khaw, S.L.; Kovar, P.J.; Lam, L.T.; Lee, J.; Maecker, H.L.; Marsh, K.C.; Mason, K.D.; Mitten, M.J.; Nimmer, P.M.; Oleksijew, A.; Park, C.H.; Park, C.M.; Phillips, D.C.; Roberts, A.W.; Sampath, D.; Seymour, J.F.; Smith, M.L.; Sullivan, G.M.; Tahir, S.K.; Tse, C.; Wendt, M.D.; Xiao, Y.; Xue, J.C.; Zhang, H.; Humerickhouse, R.A.; Rosenberg, S.H.; Elmore, S.W. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat. Med., 2013, 19(2), 202-208.
[http://dx.doi.org/10.1038/nm.3048] [PMID: 23291630]
[32]
Cang, S.; Iragavarapu, C.; Savooji, J.; Song, Y.; Liu, D. ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J. Hematol. Oncol., 2015, 8(1), 129.
[http://dx.doi.org/10.1186/s13045-015-0224-3] [PMID: 26589495]
[33]
Leverson, J.D.; Sampath, D.; Souers, A.J.; Rosenberg, S.H.; Fairbrother, W.J.; Amiot, M.; Konopleva, M.; Letai, A. Found in translation: How preclinical research is guiding the clinical development of the BCL2-selective inhibitor venetoclax. Cancer Discov., 2017, 7(12), 1376-1393.
[http://dx.doi.org/10.1158/2159-8290.CD-17-0797] [PMID: 29146569]
[34]
Erlanson, D.A.; Fesik, S.W.; Hubbard, R.E.; Jahnke, W.; Jhoti, H. Twenty years on: The impact of fragments on drug discovery. Nat. Rev. Drug Discov., 2016, 15(9), 605-619.
[http://dx.doi.org/10.1038/nrd.2016.109] [PMID: 27417849]
[35]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[36]
Siefker-Radtke, A.O.; Necchi, A.; Park, S.H.; García-Donas, J.; Huddart, R.A.; Burgess, E.F.; Fleming, M.T.; Rezazadeh Kalebasty, A.; Mellado, B.; Varlamov, S.; Joshi, M.; Duran, I.; Tagawa, S.T.; Zakharia, Y.; Akapame, S.; Santiago-Walker, A.E.; Monga, M.; O’Hagan, A.; Loriot, Y.; Necchi, A.; Loriot, Y.; Park, S.H.; Tagawa, S.; Flechon, A.; Alexeev, B.; Varlamov, S.; Huddart, R.; Burgess, E.; Rezazadeh, A.; Siefker-Radtke, A.; Vano, Y.; Gasparro, D.; Hamzaj, A.; Kopyltsov, E.; Gracia Donas, J.; Mellado, B.; Parikh, O.; Schatteman, P.; Culine, S.; Houédé, N.; Zanetta, S.; Facchini, G.; Scagliotti, G.; Schinzari, G.; Lee, J.L.; Shkolnik, M.; Fleming, M.; Joshi, M.; O’Donnell, P.; Stöger, H.; Decaestecker, K.; Dirix, L.; Machiels, J.P.; Borchiellini, D.; Delva, R.; Rolland, F.; Hadaschik, B.; Retz, M.; Rosenbaum, E.; Basso, U.; Mosca, A.; Lee, H.J.; Shin, D.B.; Cebotaru, C.; Duran, I.; Moreno, V.; Perez Gracia, J.L.; Pinto, A.; Su, W-P.; Wang, S-S.; Hainsworth, J.; Schnadig, I.; Srinivas, S.; Vogelzang, N.; Loidl, W.; Meran, J.; Gross Goupil, M.; Joly, F.; Imkamp, F.; Klotz, T.; Krege, S.; May, M.; Schultze-Seemann, W.; Strauss, A.; Zimmermann, U.; Keizman, D.; Peer, A.; Sella, A.; Berardi, R.; De Giorgi, U.; Sternberg, C.N.; Rha, S.Y.; Bulat, I.; Izmailov, A.; Matveev, V.; Vladimirov, V.; Carles, J.; Font, A.; Saez, M.; Syndikus, I.; Tarver, K.; Appleman, L.; Burke, J.; Dawson, N.; Jain, S.; Zakharia, Y. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol., 2022, 23(2), 248-258.
[http://dx.doi.org/10.1016/S1470-2045(21)00660-4] [PMID: 35030333]
[37]
Krook, M.A.; Reeser, J.W.; Ernst, G.; Barker, H.; Wilberding, M.; Li, G.; Chen, H.Z.; Roychowdhury, S. Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance. Br. J. Cancer, 2021, 124(5), 880-892.
[http://dx.doi.org/10.1038/s41416-020-01157-0] [PMID: 33268819]
[38]
Peng, J.; Sridhar, S.; Siefker-Radtke, A.O.; Selvarajah, S.; Jiang, D.M. Targeting the FGFR pathway in urothelial carcinoma: The future is now. Curr. Treat. Options Oncol., 2022, 23(9), 1269-1287.
[http://dx.doi.org/10.1007/s11864-022-01009-4] [PMID: 35962938]
[39]
Squires, M.; Ward, G.; Saxty, G.; Berdini, V.; Cleasby, A.; King, P.; Angibaud, P.; Perera, T.; Fazal, L.; Ross, D.; Jones, C.G.; Madin, A.; Benning, R.K.; Vickerstaffe, E.; O’Brien, A.; Frederickson, M.; Reader, M.; Hamlett, C.; Batey, M.A.; Rich, S.; Carr, M.; Miller, D.; Feltell, R.; Thiru, A.; Bethell, S.; Devine, L.A.; Graham, B.L.; Pike, A.; Cosme, J.; Lewis, E.J.; Freyne, E.; Lyons, J.; Irving, J.; Murray, C.; Newell, D.R.; Thompson, N.T. Potent, selective inhibitors of fibroblast growth factor receptor define fibroblast growth factor dependence in preclinical cancer models. Mol. Cancer Ther., 2011, 10(9), 1542-1552.
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0426] [PMID: 21764904]
[40]
Murray, C.W.; Newell, D.R.; Angibaud, P. A successful collaboration between academia, biotech and pharma led to discovery of erdafitinib, a selective FGFR inhibitor recently approved by the FDA. MedChemComm, 2019, 10(9), 1509-1511.
[http://dx.doi.org/10.1039/C9MD90044F]
[41]
El Newahie, A.M.S.; Ismail, N.S.M.; Abou El Ella, D.A.; Abouzid, K.A.M. Quinoxaline-based scaffolds targeting tyrosine kinases and their potential anticancer activity: Quinoxaline-based scaffolds targeting tyrosine kinases. Arch. Pharm., 2016, 349(5), 309-326.
[http://dx.doi.org/10.1002/ardp.201500468] [PMID: 27062086]
[42]
Kumar, V.; Kaur, N.; Sahu, S. Role of tyrosine kinases and their inhibitors in cancer therapy: A comprehensive review. Curr. Med. Chem., 2022, 30(13), 1464-1481.
[http://dx.doi.org/10.2174/0929867329666220727122952]
[43]
Rees, D.C. Medicines for millions of patients. RSC Med. Chem., 2022, 13(1), 7-12.
[http://dx.doi.org/10.1039/D1MD00279A] [PMID: 35211673]
[44]
Nishina, T.; Takahashi, S.; Iwasawa, R.; Noguchi, H.; Aoki, M.; Doi, T. Safety, pharmacokinetic, and pharmacodynamics of erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, in patients with advanced or refractory solid tumors. Invest. New Drugs, 2018, 36(3), 424-434.
[http://dx.doi.org/10.1007/s10637-017-0514-4] [PMID: 28965185]
[45]
Perera, T.P.S.; Jovcheva, E.; Mevellec, L.; Vialard, J.; De Lange, D.; Verhulst, T.; Paulussen, C.; Van De Ven, K.; King, P.; Freyne, E.; Rees, D.C.; Squires, M.; Saxty, G.; Page, M.; Murray, C.W.; Gilissen, R.; Ward, G.; Thompson, N.T.; Newell, D.R.; Cheng, N.; Xie, L.; Yang, J.; Platero, S.J.; Karkera, J.D.; Moy, C.; Angibaud, P.; Laquerre, S.; Lorenzi, M.V. Discovery and pharmacological characterization of JNJ-42756493 (erdafitinib), a functionally selective small-molecule FGFR family inhibitor. Mol. Cancer Ther., 2017, 16(6), 1010-1020.
[http://dx.doi.org/10.1158/1535-7163.MCT-16-0589] [PMID: 28341788]
[46]
Bansal, P.; Dwivedi, D.K.; Hatwal, D.; Sharma, P.; Gupta, V.; Goyal, S.; Maithani, M. Erdafitinib as a novel and advanced treatment strategy of metastatic urothelial carcinoma. Anticancer. Agents Med. Chem., 2021, 21(18), 2478-2486.
[http://dx.doi.org/10.2174/1871520621666210121093852] [PMID: 33475078]
[47]
Spierenburg, G.; van der Heijden, L.; van Langevelde, K.; Szuhai, K.; Bovée, J.V.G.M.; van de Sande, M.A.J.; Gelderblom, H. Tenosynovial giant cell tumors (TGCT): Molecular biology, drug targets and non-surgical pharmacological approaches. Expert Opin. Ther. Targets, 2022, 26(4), 333-345.
[http://dx.doi.org/10.1080/14728222.2022.2067040] [PMID: 35443852]
[48]
Dupont, C.A.; Riegel, K.; Pompaiah, M.; Juhl, H.; Rajalingam, K. Druggable genome and precision medicine in cancer: current challenges. FEBS J., 2021, 288(21), 6142-6158.
[http://dx.doi.org/10.1111/febs.15788] [PMID: 33626231]
[49]
Wen, J.; Wang, S.; Guo, R.; Liu, D. CSF1R inhibitors are emerging immunotherapeutic drugs for cancer treatment. Eur. J. Med. Chem., 2023, 245(Pt 1), 114884.
[http://dx.doi.org/10.1016/j.ejmech.2022.114884] [PMID: 36335744]
[50]
Palmerini, E.; Staals, E.L. Treatment updates on tenosynovial giant cell tumor. Curr. Opin. Oncol., 2022, 34(4), 322-327.
[http://dx.doi.org/10.1097/CCO.0000000000000853] [PMID: 35837703]
[51]
Zhang, C.; Ibrahim, P.N.; Zhang, J.; Burton, E.A.; Habets, G.; Zhang, Y.; Powell, B.; West, B.L.; Matusow, B.; Tsang, G.; Shellooe, R.; Carias, H.; Nguyen, H.; Marimuthu, A.; Zhang, K.Y.J.; Oh, A.; Bremer, R.; Hurt, C.R.; Artis, D.R.; Wu, G.; Nespi, M.; Spevak, W.; Lin, P.; Nolop, K.; Hirth, P.; Tesch, G.H.; Bollag, G. Design and pharmacology of a highly specific dual FMS and KIT kinase inhibitor. Proc. Natl. Acad. Sci. USA, 2013, 110(14), 5689-5694.
[http://dx.doi.org/10.1073/pnas.1219457110] [PMID: 23493555]
[52]
Tap, W.D.; Wainberg, Z.A.; Anthony, S.P.; Ibrahim, P.N.; Zhang, C.; Healey, J.H.; Chmielowski, B.; Staddon, A.P.; Cohn, A.L.; Shapiro, G.I.; Keedy, V.L.; Singh, A.S.; Puzanov, I.; Kwak, E.L.; Wagner, A.J.; Von Hoff, D.D.; Weiss, G.J.; Ramanathan, R.K.; Zhang, J.; Habets, G.; Zhang, Y.; Burton, E.A.; Visor, G.; Sanftner, L.; Severson, P.; Nguyen, H.; Kim, M.J.; Marimuthu, A.; Tsang, G.; Shellooe, R.; Gee, C.; West, B.L.; Hirth, P.; Nolop, K.; van de Rijn, M.; Hsu, H.H.; Peterfy, C.; Lin, P.S.; Tong-Starksen, S.; Bollag, G. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N. Engl. J. Med., 2015, 373(5), 428-437.
[http://dx.doi.org/10.1056/NEJMoa1411366] [PMID: 26222558]
[53]
Alsayadi, Y.M.M.A.; Chawla, P.A. Prospects of treating tenosynovial giant cell tumor through pexidartinib: A review. Anticancer. Agents Med. Chem., 2021, 21(12), 1510-1519.
[http://dx.doi.org/10.2174/1871520620999201102123555] [PMID: 33143617]
[54]
Benner, B.; Good, L.; Quiroga, D.; Schultz, T.E.; Kassem, M.; Carson, W.E.; Cherian, M.A.; Sardesai, S.; Wesolowski, R. Pexidartinib, a novel small molecule CSF-1R inhibitor in use for tenosynovial giant cell tumor: A systematic review of pre-clinical and clinical development. Drug Des. Devel. Ther., 2020, 14, 1693-1704.
[http://dx.doi.org/10.2147/DDDT.S253232] [PMID: 32440095]
[55]
Liang, X.; Wu, P.; Yang, Q.; Xie, Y.; He, C.; Yin, L.; Yin, Z.; Yue, G.; Zou, Y.; Li, L.; Song, X.; Lv, C.; Zhang, W.; Jing, B. An update of new small-molecule anticancer drugs approved from 2015 to 2020. Eur. J. Med. Chem., 2021, 220, 113473.
[http://dx.doi.org/10.1016/j.ejmech.2021.113473] [PMID: 33906047]
[56]
Rio-Vilariño, A.; del Puerto-Nevado, L.; García-Foncillas, J.; Cebrián, A. Ras family of small GTPases in CRC: New perspectives for overcoming drug resistance. Cancers (Basel), 2021, 13(15), 3757.
[http://dx.doi.org/10.3390/cancers13153757] [PMID: 34359657]
[57]
Sheffels, E.; Kortum, R.L. The role of wild-type RAS in oncogenic RAS transformation. Genes, 2021, 12(5), 662.
[http://dx.doi.org/10.3390/genes12050662]
[58]
Erlanson, D.A.; Webster, K.R. Targeting mutant KRAS. Curr. Opin. Chem. Biol., 2021, 62, 101-108.
[http://dx.doi.org/10.1016/j.cbpa.2021.02.010] [PMID: 33838397]
[59]
Li, H-Y.; Qi, W-L.; Wang, Y-X. Covalent inhibitor targets KRasG12C: A new paradigm for drugging the undruggable and challenges ahead. Genes Dis., 2021. Epub ahead of print
[http://dx.doi.org/10.1016/j.gendis.2021.08.011]
[60]
Ostrem, J.M.; Peters, U.; Sos, M.L.; Wells, J.A.; Shokat, K.M. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature, 2013, 503(7477), 548-551.
[http://dx.doi.org/10.1038/nature12796] [PMID: 24256730]
[61]
Janes, M.R.; Zhang, J.; Li, L.S.; Hansen, R.; Peters, U.; Guo, X.; Chen, Y.; Babbar, A.; Firdaus, S.J.; Darjania, L.; Feng, J.; Chen, J.H.; Li, S.; Li, S.; Long, Y.O.; Thach, C.; Liu, Y.; Zarieh, A.; Ely, T.; Kucharski, J.M.; Kessler, L.V.; Wu, T.; Yu, K.; Wang, Y.; Yao, Y.; Deng, X.; Zarrinkar, P.P.; Brehmer, D.; Dhanak, D.; Lorenzi, M.V.; Hu-Lowe, D.; Patricelli, M.P.; Ren, P.; Liu, Y. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell, 2018, 172(3), 578-589.e17.
[http://dx.doi.org/10.1016/j.cell.2018.01.006] [PMID: 29373830]
[62]
Shin, Y.; Jeong, J.W.; Wurz, R.P.; Achanta, P.; Arvedson, T.; Bartberger, M.D.; Campuzano, I.D.G.; Fucini, R.; Hansen, S.K.; Ingersoll, J.; Iwig, J.S.; Lipford, J.R.; Ma, V.; Kopecky, D.J.; McCarter, J.; San Miguel, T.; Mohr, C.; Sabet, S.; Saiki, A.Y.; Sawayama, A.; Sethofer, S.; Tegley, C.M.; Volak, L.P.; Yang, K.; Lanman, B.A.; Erlanson, D.A.; Cee, V.J. Discovery of N -(1-Acryloylazetidin-3-yl)-2-(1 H -indol-1-yl)acetamides as Covalent Inhibitors of KRAS G12C. ACS Med. Chem. Lett., 2019, 10(9), 1302-1308.
[http://dx.doi.org/10.1021/acsmedchemlett.9b00258] [PMID: 31531201]
[63]
Lanman, B.A.; Allen, J.R.; Allen, J.G.; Amegadzie, A.K.; Ashton, K.S.; Booker, S.K.; Chen, J.J.; Chen, N.; Frohn, M.J.; Goodman, G.; Kopecky, D.J.; Liu, L.; Lopez, P.; Low, J.D.; Ma, V.; Minatti, A.E.; Nguyen, T.T.; Nishimura, N.; Pickrell, A.J.; Reed, A.B.; Shin, Y.; Siegmund, A.C.; Tamayo, N.A.; Tegley, C.M.; Walton, M.C.; Wang, H.L.; Wurz, R.P.; Xue, M.; Yang, K.C.; Achanta, P.; Bartberger, M.D.; Canon, J.; Hollis, L.S.; McCarter, J.D.; Mohr, C.; Rex, K.; Saiki, A.Y.; San, M.T.; Volak, L.P.; Wang, K.H.; Whittington, D.A.; Zech, S.G.; Lipford, J.R.; Cee, V.J. Discovery of a covalent inhibitor of KRASG12C (AMG 510) for the treatment of solid tumors. J. Med. Chem., 2020, 63(1), 52-65.
[http://dx.doi.org/10.1021/acs.jmedchem.9b01180] [PMID: 31820981]
[64]
Blair, H.A. Sotorasib: First Approval. Drugs, 2021, 81(13), 1573-1579.
[http://dx.doi.org/10.1007/s40265-021-01574-2] [PMID: 34357500]
[65]
Deeks, E.D. Asciminib: First Approval. Drugs, 2022, 82(2), 219-226.
[http://dx.doi.org/10.1007/s40265-021-01662-3] [PMID: 35041175]
[66]
Schoepfer, J.; Jahnke, W.; Berellini, G.; Buonamici, S.; Cotesta, S.; Cowan-Jacob, S.W.; Dodd, S.; Drueckes, P.; Fabbro, D.; Gabriel, T.; Groell, J.M.; Grotzfeld, R.M.; Hassan, A.Q.; Henry, C.; Iyer, V.; Jones, D.; Lombardo, F.; Loo, A.; Manley, P.W.; Pellé, X.; Rummel, G.; Salem, B.; Warmuth, M.; Wylie, A.A.; Zoller, T.; Marzinzik, A.L.; Furet, P. Discovery of asciminib(ABL001), an allosteric inhibitor of the tyrosine kinase activity of BCR-ABL1. J. Med. Chem., 2018, 61(18), 8120-8135.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01040] [PMID: 30137981]
[67]
Cohen, P.; Cross, D.; Jänne, P.A. Kinase drug discovery 20 years after imatinib: Progress and future directions. Nat. Rev. Drug Discov., 2021, 20(7), 551-569.
[http://dx.doi.org/10.1038/s41573-021-00195-4] [PMID: 34002056]
[68]
Réa, D.; Hughes, T.P. Development of asciminib, a novel allosteric inhibitor of BCR-ABL1. Crit. Rev. Oncol. Hematol., 2022, 171, 103580.
[http://dx.doi.org/10.1016/j.critrevonc.2022.103580] [PMID: 35021069]
[69]
Nagar, B.; Hantschel, O.; Young, M.A.; Scheffzek, K.; Veach, D.; Bornmann, W.; Clarkson, B.; Superti-Furga, G.; Kuriyan, J. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell, 2003, 112(6), 859-871.
[http://dx.doi.org/10.1016/S0092-8674(03)00194-6] [PMID: 12654251]
[70]
Hantschel, O.; Nagar, B.; Guettler, S.; Kretzschmar, J.; Dorey, K.; Kuriyan, J.; Superti-Furga, G. A myristoyl/phosphotyrosine switch regulates c-Abl. Cell, 2003, 112(6), 845-857.
[http://dx.doi.org/10.1016/S0092-8674(03)00191-0] [PMID: 12654250]
[71]
Adrián, F.J.; Ding, Q.; Sim, T.; Velentza, A.; Sloan, C.; Liu, Y.; Zhang, G.; Hur, W.; Ding, S.; Manley, P.; Mestan, J.; Fabbro, D.; Gray, N.S. Allosteric inhibitors of Bcr-abl–dependent cell proliferation. Nat. Chem. Biol., 2006, 2(2), 95-102.
[http://dx.doi.org/10.1038/nchembio760] [PMID: 16415863]
[72]
Schiffer, C.A. Asciminib for CML: Same target, new arrow. Blood, 2021, 138(21), 2009-2010.
[http://dx.doi.org/10.1182/blood.2021013257] [PMID: 34821938]
[73]
Addie, M.; Ballard, P.; Buttar, D.; Crafter, C.; Currie, G.; Davies, B.R.; Debreczeni, J.; Dry, H.; Dudley, P.; Greenwood, R.; Johnson, P.D.; Kettle, J.G.; Lane, C.; Lamont, G.; Leach, A.; Luke, R.W.A.; Morris, J.; Ogilvie, D.; Page, K.; Pass, M.; Pearson, S.; Ruston, L. Discovery of 4-Amino- N -[(1 S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7 H -pyrrolo[2,3- d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases. J. Med. Chem., 2013, 56(5), 2059-2073.
[http://dx.doi.org/10.1021/jm301762v] [PMID: 23394218]
[74]
Siu, K.T.; Ramachandran, J.; Yee, A.J.; Eda, H.; Santo, L.; Panaroni, C.; Mertz, J.A.; Sims, R.J., III; Cooper, M.R.; Raje, N. Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma. Leukemia, 2017, 31(8), 1760-1769.
[http://dx.doi.org/10.1038/leu.2016.355] [PMID: 27890933]
[75]
Gehling, V.S.; Hewitt, M.C.; Vaswani, R.G.; Leblanc, Y.; Côté, A.; Nasveschuk, C.G.; Taylor, A.M.; Harmange, J.C.; Audia, J.E.; Pardo, E.; Joshi, S.; Sandy, P.; Mertz, J.A.; Sims, R.J., III; Bergeron, L.; Bryant, B.M.; Bellon, S.; Poy, F.; Jayaram, H.; Sankaranarayanan, R.; Yellapantula, S.; Bangalore Srinivasamurthy, N.; Birudukota, S.; Albrecht, B.K. Discovery, design, and optimization of isoxazole azepine BET inhibitors. ACS Med. Chem. Lett., 2013, 4(9), 835-840.
[http://dx.doi.org/10.1021/ml4001485] [PMID: 24900758]
[76]
Mullard, A. Antibody clamps pry open small-molecule drug discovery opportunities. Nat. Rev. Drug Discov., 2022, 21(4), 247-248.
[http://dx.doi.org/10.1038/d41573-022-00054-w] [PMID: 35288684]
[77]
Brown, A.J.H.; Bradley, S.J.; Marshall, F.H.; Brown, G.A.; Bennett, K.A.; Brown, J.; Cansfield, J.E.; Cross, D.M.; de Graaf, C.; Hudson, B.D.; Dwomoh, L.; Dias, J.M.; Errey, J.C.; Hurrell, E.; Liptrot, J.; Mattedi, G.; Molloy, C.; Nathan, P.J.; Okrasa, K.; Osborne, G.; Patel, J.C.; Pickworth, M.; Robertson, N.; Shahabi, S.; Bundgaard, C.; Phillips, K.; Broad, L.M.; Goonawardena, A.V.; Morairty, S.R.; Browning, M.; Perini, F.; Dawson, G.R.; Deakin, J.F.W.; Smith, R.T.; Sexton, P.M.; Warneck, J.; Vinson, M.; Tasker, T.; Tehan, B.G.; Teobald, B.; Christopoulos, A.; Langmead, C.J.; Jazayeri, A.; Cooke, R.M.; Rucktooa, P.; Congreve, M.S.; Weir, M.; Tobin, A.B. From structure to clinic: Design of a muscarinic M1 receptor agonist with the potential to treat Alzheimer’s disease. Cell, 2021, 184(24), 5886-5901.e22.
[http://dx.doi.org/10.1016/j.cell.2021.11.001] [PMID: 34822784]
[78]
Markert, C.; Thoma, G.; Srinivas, H.; Bollbuck, B.; Lüönd, R.M.; Miltz, W.; Wälchli, R.; Wolf, R.; Hinrichs, J.; Bergsdorf, C.; Azzaoui, K.; Penno, C.A.; Klein, K.; Wack, N.; Jäger, P.; Hasler, F.; Beerli, C.; Loetscher, P.; Dawson, J.; Wieczorek, G.; Numao, S.; Littlewood-Evans, A.; Röhn, T.A. Discovery of LYS006, a potent and highly selective inhibitor of leukotriene A4 hydrolase. J. Med. Chem., 2021, 64(4), 1889-1903.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01955] [PMID: 33592148]
[79]
Lee, K.L.; Ambler, C.M.; Anderson, D.R.; Boscoe, B.P.; Bree, A.G.; Brodfuehrer, J.I.; Chang, J.S.; Choi, C.; Chung, S.; Curran, K.J.; Day, J.E.; Dehnhardt, C.M.; Dower, K.; Drozda, S.E.; Frisbie, R.K.; Gavrin, L.K.; Goldberg, J.A.; Han, S.; Hegen, M.; Hepworth, D.; Hope, H.R.; Kamtekar, S.; Kilty, I.C.; Lee, A.; Lin, L.L.; Lovering, F.E.; Lowe, M.D.; Mathias, J.P.; Morgan, H.M.; Murphy, E.A.; Papaioannou, N.; Patny, A.; Pierce, B.S.; Rao, V.R.; Saiah, E.; Samardjiev, I.J.; Samas, B.M.; Shen, M.W.H.; Shin, J.H.; Soutter, H.H.; Strohbach, J.W.; Symanowicz, P.T.; Thomason, J.R.; Trzupek, J.D.; Vargas, R.; Vincent, F.; Yan, J.; Zapf, C.W.; Wright, S.W. Discovery of Clinical Candidate 1-[(2 S, 3 S, 4 S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a potent, selective inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4), by fragment-based drug design. J. Med. Chem., 2017, 60(13), 5521-5542.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00231] [PMID: 28498658]
[80]
Messick, T.E.; Smith, G.R.; Soldan, S.S.; McDonnell, M.E.; Deakyne, J.S.; Malecka, K.A.; Tolvinski, L.; van den Heuvel, A.P.J.; Gu, B.W.; Cassel, J.A.; Tran, D.H.; Wassermann, B.R.; Zhang, Y.; Velvadapu, V.; Zartler, E.R.; Busson, P.; Reitz, A.B.; Lieberman, P.M. Structure-based design of small-molecule inhibitors of EBNA1 DNA binding blocks Epstein-Barr virus latent infection and tumor growth. Sci. Transl. Med., 2019, 11(482), eaau5612.
[http://dx.doi.org/10.1126/scitranslmed.aau5612] [PMID: 30842315]
[81]
Maragno, A.L.; Mistry, P.; Kotschy, A. Abstract 4482: S64315 (MIK665) is a potent and selective Mcl1 inhibitor with strong antitumor activity across a diverse range of hematologic tumor models. In: Exper. Mol. Therap; American Association for Cancer Research, 2019.
[http://dx.doi.org/10.1158/1538-7445.AM2019-4482]
[82]
Reich, S.H.; Sprengeler, P.A.; Chiang, G.G.; Appleman, J.R.; Chen, J.; Clarine, J.; Eam, B.; Ernst, J.T.; Han, Q.; Goel, V.K.; Han, E.Z.R.; Huang, V.; Hung, I.N.J.; Jemison, A.; Jessen, K.A.; Molter, J.; Murphy, D.; Neal, M.; Parker, G.S.; Shaghafi, M.; Sperry, S.; Staunton, J.; Stumpf, C.R.; Thompson, P.A.; Tran, C.; Webber, S.E.; Wegerski, C.J.; Zheng, H.; Webster, K.R. Structure-based design of pyridone–aminal eFT508 targeting dysregulated translation by selective mitogen-activated protein kinase interacting kinases 1 and 2(MNK1/2) inhibition. J. Med. Chem., 2018, 61(8), 3516-3540.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01795] [PMID: 29526098]
[83]
Tron, A.E.; Belmonte, M.A.; Adam, A.; Aquila, B.M.; Boise, L.H.; Chiarparin, E.; Cidado, J.; Embrey, K.J.; Gangl, E.; Gibbons, F.D.; Gregory, G.P.; Hargreaves, D.; Hendricks, J.A.; Johannes, J.W.; Johnstone, R.W.; Kazmirski, S.L.; Kettle, J.G.; Lamb, M.L.; Matulis, S.M.; Nooka, A.K.; Packer, M.J.; Peng, B.; Rawlins, P.B.; Robbins, D.W.; Schuller, A.G.; Su, N.; Yang, W.; Ye, Q.; Zheng, X.; Secrist, J.P.; Clark, E.A.; Wilson, D.M.; Fawell, S.E.; Hird, A.W. Discovery of Mcl-1-specific inhibitor AZD5991 and preclinical activity in multiple myeloma and acute myeloid leukemia. Nat. Commun., 2018, 9(1), 5341.
[http://dx.doi.org/10.1038/s41467-018-07551-w] [PMID: 30559424]
[84]
Johnson, C.N.; Ahn, J.S.; Buck, I.M.; Chiarparin, E.; Day, J.E.H.; Hopkins, A.; Howard, S.; Lewis, E.J.; Martins, V.; Millemaggi, A.; Munck, J.M.; Page, L.W.; Peakman, T.; Reader, M.; Rich, S.J.; Saxty, G.; Smyth, T.; Thompson, N.T.; Ward, G.A.; Williams, P.A.; Wilsher, N.E.; Chessari, G. A fragment-derived clinical candidate for antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H, 2 H, 3 H -pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R, 5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660). J. Med. Chem., 2018, 61(16), 7314-7329.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00900] [PMID: 30091600]
[85]
Munck, J.M.; Berdini, V.; Bevan, L.; Brothwood, J.L.; Castro, J.; Courtin, A.; East, C.; Ferraldeschi, R.; Heightman, T.D.; Hindley, C.J.; Kucia-Tran, J.; Lyons, J.F.; Martins, V.; Muench, S.; Murray, C.W.; Norton, D.; O’Reilly, M.; Reader, M.; Rees, D.C.; Rich, S.J.; Richardson, C.J.; Shah, A.D.; Stanczuk, L.; Thompson, N.T.; Wilsher, N.E.; Woolford, A.J.A.; Wallis, N.G. ASTX029, a novel dual-mechanism ERK inhibitor, modulates both the phosphorylation and catalytic activity of ERK. Mol. Cancer Ther., 2021, 20(10), 1757-1768.
[http://dx.doi.org/10.1158/1535-7163.MCT-20-0909] [PMID: 34330842]
[86]
Smith, C.R.; Aranda, R.; Bobinski, T.P.; Briere, D.M.; Burns, A.C.; Christensen, J.G.; Clarine, J.; Engstrom, L.D.; Gunn, R.J.; Ivetac, A.; Jean-Baptiste, R.; Ketcham, J.M.; Kobayashi, M.; Kuehler, J.; Kulyk, S.; Lawson, J.D.; Moya, K.; Olson, P.; Rahbaek, L.; Thomas, N.C.; Wang, X.; Waters, L.M.; Marx, M.A. Fragment-based discovery of MRTX1719, a synthetic lethal inhibitor of the PRMT5•MTA complex for the treatment of MTAP-deleted cancers. J. Med. Chem., 2022, 65(3), 1749-1766.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01900] [PMID: 35041419]
[87]
Konteatis, Z.; Travins, J.; Gross, S.; Marjon, K.; Barnett, A.; Mandley, E.; Nicolay, B.; Nagaraja, R.; Chen, Y.; Sun, Y.; Liu, Z.; Yu, J.; Ye, Z.; Jiang, F.; Wei, W.; Fang, C.; Gao, Y.; Kalev, P.; Hyer, M.L.; DeLaBarre, B.; Jin, L.; Padyana, A.K.; Dang, L.; Murtie, J.; Biller, S.A.; Sui, Z.; Marks, K.M. Discovery of AG-270, a first-in-class oral MAT2A inhibitor for the treatment of tumors with homozygous MTAP deletion. J. Med. Chem., 2021, 64(8), 4430-4449.
[http://dx.doi.org/10.1021/acs.jmedchem.0c01895] [PMID: 33829783]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy