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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

The Structure–property Relationships of Clinically Approved Protein Kinase Inhibitors

Author(s): Kihang Choi

Volume 30, Issue 22, 2023

Published on: 24 October, 2022

Page: [2518 - 2541] Pages: 24

DOI: 10.2174/0929867329666220822123552

Price: $65

Abstract

Background: Protein kinase inhibitors have become one of the most successful classes of small-molecule drugs during the last decades. In modern drug discovery, considering ‘drug-like’ physicochemical and pharmacokinetic properties as early as possible in drug design is widely acknowledged as an important strategy to reduce drug attrition rates.

Methods: In this review, clinically approved 25 protein kinase inhibitors and their key analogues reported in medicinal chemistry literature were compared for their biological, physicochemical, and pharmacokinetic properties. Although there is no common trajectory to follow through complex drug discovery campaigns, knowledge of the structure– activity relationship obtained from the successful lead optimization studies might be extended to other drug design efforts.

Results: Among more than 70 protein kinase inhibitors clinically approved around the world, the structure–activity relationships of 25 inhibitors and their key analogues are compiled from medicinal chemistry literature, in which detailed results from the ‘lead-tocandidate’ stage are available with associated property data. For the other inhibitors, such information has not been disclosed in the literature, or the available data is limited and not sufficient to provide clear structural analysis.

Conclusion: The structure–property relationships summarized for 25 inhibitors and their analogues illustrate general guidelines for lead optimization and candidate selection, and this information could be extended for better property-based drug design in the future.

Keywords: Structure–property relationship, protein kinase inhibitors, solubilizing groups, lead optimization, candidate selection, drug discovery.

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[1]
Paul, S.M.; Mytelka, D.S.; Dunwiddie, C.T.; Persinger, C.C.; Munos, B.H.; Lindborg, S.R.; Schacht, A.L. How to improve R&D productivity: The pharmaceutical industry’s grand challenge. Nat. Rev. Drug Discov., 2010, 9(3), 203-214.
[http://dx.doi.org/10.1038/nrd3078] [PMID: 20168317]
[2]
Wagner, J.; Dahlem, A.M.; Hudson, L.D.; Terry, S.F.; Altman, R.B.; Gilliland, C.T.; DeFeo, C.; Austin, C.P. A dynamic map for learning, communicating, navigating and improving therapeutic development. Nat. Rev. Drug Discov., 2018, 17(2), 150-150.
[http://dx.doi.org/10.1038/nrd.2017.217] [PMID: 29269942]
[3]
Veale, C.G.L. Into the fray! A beginner’s guide to medicinal chemistry. ChemMedChem, 2021, 16(8), 1199-1225.
[http://dx.doi.org/10.1002/cmdc.202000929] [PMID: 33591595]
[4]
Kenakin, T. Quantifying biological activity in chemical terms: A pharmacology primer to describe drug effect. ACS Chem. Biol., 2009, 4(4), 249-260.
[http://dx.doi.org/10.1021/cb800299s] [PMID: 19193052]
[5]
Powers, J.P.; Piper, D.E.; Li, Y.; Mayorga, V.; Anzola, J.; Chen, J.M.; Jaen, J.C.; Lee, G.; Liu, J.; Peterson, M.G.; Tonn, G.R.; Ye, Q.; Walker, N.P.C.; Wang, Z. SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase. J. Med. Chem., 2006, 49(3), 1034-1046.
[http://dx.doi.org/10.1021/jm050859x] [PMID: 16451069]
[6]
Asaki, T.; Hamamoto, T.; Sugiyama, Y.; Kuwano, K.; Kuwabara, K. Structure-activity studies on diphenylpyrazine derivatives: A novel class of prostacyclin receptor agonists. Bioorg. Med. Chem., 2007, 15(21), 6692-6704.
[http://dx.doi.org/10.1016/j.bmc.2007.08.010] [PMID: 17764960]
[7]
Procopiou, P.A.; Barrett, V.J.; Bevan, N.J.; Biggadike, K.; Box, P.C.; Butchers, P.R.; Coe, D.M.; Conroy, R.; Emmons, A.; Ford, A.J.; Holmes, D.S.; Horsley, H.; Kerr, F.; Li-Kwai-Cheung, A-M.; Looker, B.E.; Mann, I.S.; McLay, I.M.; Morrison, V.S.; Mutch, P.J.; Smith, C.E.; Tomlin, P. Synthesis and structure-activity relationships of long-acting β2 adrenergic receptor agonists incorporating metabolic inactivation: An antedrug approach. J. Med. Chem., 2010, 53(11), 4522-4530.
[http://dx.doi.org/10.1021/jm100326d] [PMID: 20462258]
[8]
Akbar, A.; McNeil, N.M.R.; Albert, M.R.; Ta, V.; Adhikary, G.; Bourgeois, K.; Eckert, R.L.; Keillor, J.W. Structure–activity relationships of potent, targeted covalent inhibitors that abolish both the transamidation and GTP binding activities of human tissue transglutaminase. J. Med. Chem., 2017, 60(18), 7910-7927.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01070] [PMID: 28858494]
[9]
Simeon, S.; Ghislat, G.; Ballester, P. Characterizing the relationship between the chemical structures of drugs and their activities on primary cultures of pediatric solid tumors. Curr. Med. Chem., 2021, 28(38), 7830-7839.
[http://dx.doi.org/10.2174/0929867328666210419134708] [PMID: 33874867]
[10]
Bancet, A.; Raingeval, C.; Lomberget, T.; Le Borgne, M.; Guichou, J-F.; Krimm, I. Fragment linking strategies for structure-based drug design. J. Med. Chem., 2020, 63(20), 11420-11435.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00242] [PMID: 32539387]
[11]
Pelay-Gimeno, M.; Glas, A.; Koch, O.; Grossmann, T.N. Structure-based design of inhibitors of protein–protein interactions: Mimicking peptide binding epitopes. Angew. Chem. Int. Ed. Engl., 2015, 54(31), 8896-8927.
[http://dx.doi.org/10.1002/anie.201412070] [PMID: 26119925]
[12]
Lonsdale, R.; Ward, R.A. Structure-based design of targeted covalent inhibitors. Chem. Soc. Rev., 2018, 47(11), 3816-3830.
[http://dx.doi.org/10.1039/C7CS00220C] [PMID: 29620097]
[13]
Viaud, J.; Zeghouf, M.; Barelli, H.; Zeeh, J-C.; Padilla, A.; Guibert, B.; Chardin, P.; Royer, C.A.; Cherfils, J.; Chavanieu, A. Structure-based discovery of an inhibitor of Arf activation by Sec7 domains through targeting of protein-protein complexes. Proc. Natl. Acad. Sci. USA, 2007, 104(25), 10370-10375.
[http://dx.doi.org/10.1073/pnas.0700773104] [PMID: 17563369]
[14]
Filgueira de Azevedo, W., Jr; Canduri, F.; Marangoni dos Santos, D.; Pereira, J.H.; Dias, M.V.; Silva, R.G.; Mendes, M.A.; Basso, L.A.; Palma, M.S.; Santos, D.S. Structural basis for inhibition of human PNP by immucillin-H. Biochem. Biophys. Res. Commun., 2003, 309(4), 917-922.
[http://dx.doi.org/10.1016/j.bbrc.2003.08.094] [PMID: 13679061]
[15]
Dias, M.V.B.; Ely, F.; Palma, M.S.; de Azevedo, W.F., Jr; Basso, L.A.; Santos, D.S. Chorismate synthase: An attractive target for drug development against orphan diseases. Curr. Drug Targets, 2007, 8(3), 437-444.
[http://dx.doi.org/10.2174/138945007780058924] [PMID: 17348836]
[16]
Kenakin, T. Predicting therapeutic value in the lead optimization phase of drug discovery. Nat. Rev. Drug Discov., 2003, 2(6), 429-438.
[http://dx.doi.org/10.1038/nrd1110] [PMID: 12776218]
[17]
Copeland, R.A.; Pompliano, D.L.; Meek, T.D. Drug-target residence time and its implications for lead optimization. Nat. Rev. Drug Discov., 2006, 5(9), 730-739.
[http://dx.doi.org/10.1038/nrd2082] [PMID: 16888652]
[18]
Jorgensen, W.L. Efficient drug lead discovery and optimization. Acc. Chem. Res., 2009, 42(6), 724-733.
[http://dx.doi.org/10.1021/ar800236t] [PMID: 19317443]
[19]
Klebe, G. Applying thermodynamic profiling in lead finding and optimization. Nat. Rev. Drug Discov., 2015, 14(2), 95-110.
[http://dx.doi.org/10.1038/nrd4486] [PMID: 25614222]
[20]
Leeson, P.D.; Springthorpe, B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat. Rev. Drug Discov., 2007, 6(11), 881-890.
[http://dx.doi.org/10.1038/nrd2445] [PMID: 17971784]
[21]
St Jean, D.J., Jr; Fotsch, C. Mitigating heterocycle metabolism in drug discovery. J. Med. Chem., 2012, 55(13), 6002-6020.
[http://dx.doi.org/10.1021/jm300343m] [PMID: 22533875]
[22]
Arnott, J.A.; Planey, S.L. The influence of lipophilicity in drug discovery and design. Expert Opin. Drug Discov., 2012, 7(10), 863-875.
[http://dx.doi.org/10.1517/17460441.2012.714363] [PMID: 22992175]
[23]
Pammolli, F.; Magazzini, L.; Riccaboni, M. The productivity crisis in pharmaceutical R&D. Nat. Rev. Drug Discov., 2011, 10(6), 428-438.
[http://dx.doi.org/10.1038/nrd3405] [PMID: 21629293]
[24]
Wagner, J.A.; Dahlem, A.M.; Hudson, L.D.; Terry, S.F.; Altman, R.B.; Gilliland, C.T.; DeFeo, C.; Austin, C.P. Application of a dynamic map for learning, communicating, navigating, and improving therapeutic development. Clin. Transl. Sci., 2018, 11(2), 166-174.
[http://dx.doi.org/10.1111/cts.12531] [PMID: 29271559]
[25]
Attwood, M.M.; Fabbro, D.; Sokolov, A.V.; Knapp, S.; Schiöth, H.B. Trends in kinase drug discovery: Targets, indications and inhibitor design. Nat. Rev. Drug Discov., 2021, 20(11), 839-861.
[http://dx.doi.org/10.1038/s41573-021-00252-y] [PMID: 34354255]
[26]
Zarrin, A.A.; Bao, K.; Lupardus, P.; Vucic, D. Kinase inhibition in autoimmunity and inflammation. Nat. Rev. Drug Discov., 2021, 20(1), 39-63.
[http://dx.doi.org/10.1038/s41573-020-0082-8] [PMID: 33077936]
[27]
Zheng, J.; Wu, J.; Ding, X.; Shen, H.C.; Zou, G. Small molecule approaches to treat autoimmune and inflammatory diseases (Part I): Kinase inhibitors. Bioorg. Med. Chem. Lett., 2021, 38, 127862.
[http://dx.doi.org/10.1016/j.bmcl.2021.127862] [PMID: 33609659]
[28]
Laufer, S.; Bajorath, J. New horizons in drug discovery - understanding and advancing different types of kinase inhibitors: Seven years in kinase inhibitor research with impressive achievements and new future prospects. J. Med. Chem., 2022, 65(2), 891-892.
[http://dx.doi.org/10.1021/acs.jmedchem.1c02126] [PMID: 34941238]
[29]
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]
[30]
Ayala-Aguilera, C.C.; Valero, T.; Lorente-Macías, Á.; Baillache, D.J.; Croke, S.; Unciti-Broceta, A. Small molecule kinase inhibitor drugs (1995–2021): Medical indication, pharmacology, and synthesis. J. Med. Chem., 2022, 65(2), 1047-1131.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00963] [PMID: 34624192]
[31]
Roskoski, R., Jr Properties of FDA-approved small molecule protein kinase inhibitors: A 2022 update. Pharmacol. Res., 2022, 175, 106037.
[http://dx.doi.org/10.1016/j.phrs.2021.106037] [PMID: 34921994]
[32]
Paliouras, S.; Pearson, A.; Barkalow, F. The most successful oncology drug portfolios of the past decade. Nat. Rev. Drug Discov., 2021, 20(11), 811-812.
[http://dx.doi.org/10.1038/d41573-021-00022-w] [PMID: 33536658]
[33]
Cristina Mendonça Nogueira, T.; Vinicius Nora de Souza, M. New FDA oncology small molecule drugs approvals in 2020: Mechanism of action and clinical applications. Bioorg. Med. Chem., 2021, 46, 116340.
[http://dx.doi.org/10.1016/j.bmc.2021.116340] [PMID: 34416511]
[34]
Lu, X.; Smaill, J.B.; Ding, K. Medicinal chemistry strategies for the development of kinase inhibitors targeting point mutations. J. Med. Chem., 2020, 63(19), 10726-10741.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00507] [PMID: 32432477]
[35]
Ward, R.A.; Fawell, S.; Floc’h, N.; Flemington, V.; McKerrecher, D.; Smith, P.D. Challenges and opportunities in cancer drug resistance. Chem. Rev., 2021, 121(6), 3297-3351.
[http://dx.doi.org/10.1021/acs.chemrev.0c00383] [PMID: 32692162]
[36]
Zanforlin, E.; Zagotto, G.; Ribaudo, G. A chemical approach to overcome tyrosine kinase inhibitors resistance: Learning from chronic myeloid leukemia. Curr. Med. Chem., 2019, 26(33), 6033-6052.
[http://dx.doi.org/10.2174/0929867325666180607092451] [PMID: 29874990]
[37]
Barker, A.J.; Gibson, K.H.; Grundy, W.; Godfrey, A.A.; Barlow, J.J.; Healy, M.P.; Woodburn, J.R.; Ashton, S.E.; Curry, B.J.; Scarlett, L.; Henthorn, L.; Richards, L. Studies leading to the identification of ZD1839 (IRESSA): An orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor targeted to the treatment of cancer. Bioorg. Med. Chem. Lett., 2001, 11(14), 1911-1914.
[http://dx.doi.org/10.1016/S0960-894X(01)00344-4] [PMID: 11459659]
[38]
Yun, C-H.; Boggon, T.J.; Li, Y.; Woo, M.S.; Greulich, H.; Meyerson, M.; Eck, M.J. Structures of lung cancer-derived EGFR mutants and inhibitor complexes: Mechanism of activation and insights into differential inhibitor sensitivity. Cancer Cell, 2007, 11(3), 217-227.
[http://dx.doi.org/10.1016/j.ccr.2006.12.017] [PMID: 17349580]
[39]
Ward, R.A.; Anderton, M.J.; Ashton, S.; Bethel, P.A.; Box, M.; Butterworth, S.; Colclough, N.; Chorley, C.G.; Chuaqui, C.; Cross, D.A.E.; Dakin, L.A.; Debreczeni, J.É.; Eberlein, C.; Finlay, M.R.V.; Hill, G.B.; Grist, M.; Klinowska, T.C.M.; Lane, C.; Martin, S.; Orme, J.P.; Smith, P.; Wang, F.; Waring, M.J. Structure- and reactivity-based development of covalent inhibitors of the activating and gatekeeper mutant forms of the epidermal growth factor receptor (EGFR). J. Med. Chem., 2013, 56(17), 7025-7048.
[http://dx.doi.org/10.1021/jm400822z] [PMID: 23930994]
[40]
Finlay, M.R.V.; Anderton, M.; Ashton, S.; Ballard, P.; Bethel, P.A.; Box, M.R.; Bradbury, R.H.; Brown, S.J.; Butterworth, S.; Campbell, A.; Chorley, C.; Colclough, N.; Cross, D.A.E.; Currie, G.S.; Grist, M.; Hassall, L.; Hill, G.B.; James, D.; James, M.; Kemmitt, P.; Klinowska, T.; Lamont, G.; Lamont, S.G.; Martin, N.; McFarland, H.L.; Mellor, M.J.; Orme, J.P.; Perkins, D.; Perkins, P.; Richmond, G.; Smith, P.; Ward, R.A.; Waring, M.J.; Whittaker, D.; Wells, S.; Wrigley, G.L. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J. Med. Chem., 2014, 57(20), 8249-8267.
[http://dx.doi.org/10.1021/jm500973a] [PMID: 25271963]
[41]
Yan, X-E.; Ayaz, P.; Zhu, S-J.; Zhao, P.; Liang, L.; Zhang, C.H.; Wu, Y-C.; Li, J-L.; Choi, H.G.; Huang, X.; Shan, Y.; Shaw, D.E.; Yun, C-H. Structural basis of AZD9291 selectivity for EGFR T790M. J. Med. Chem., 2020, 63(15), 8502-8511.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00891] [PMID: 32672461]
[42]
Sun, L.; Tran, N.; Tang, F.; App, H.; Hirth, P.; McMahon, G.; Tang, C. Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases. J. Med. Chem., 1998, 41(14), 2588-2603.
[http://dx.doi.org/10.1021/jm980123i] [PMID: 9651163]
[43]
Sun, L.; Tran, N.; Liang, C.; Tang, F.; Rice, A.; Schreck, R.; Waltz, K.; Shawver, L.K.; McMahon, G.; Tang, C. Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. J. Med. Chem., 1999, 42(25), 5120-5130.
[http://dx.doi.org/10.1021/jm9904295] [PMID: 10602697]
[44]
Sun, L.; Liang, C.; Shirazian, S.; Zhou, Y.; Miller, T.; Cui, J.; Fukuda, J.Y.; Chu, J-Y.; Nematalla, A.; Wang, X.; Chen, H.; Sistla, A.; Luu, T.C.; Tang, F.; Wei, J.; Tang, C. Discovery of 5-[5-fluoro-2-oxo-1,2- dihydroindol-(3Z)-ylidenemethyl]-2,4- dimethyl-1H-pyrrole-3-carboxylic acid (2-diethylaminoethyl)amide, a novel tyrosine kinase inhibitor targeting vascular endothelial and platelet-derived growth factor receptor tyrosine kinase. J. Med. Chem., 2003, 46(7), 1116-1119.
[http://dx.doi.org/10.1021/jm0204183] [PMID: 12646019]
[45]
McTigue, M.; Murray, B.W.; Chen, J.H.; Deng, Y-L.; Solowiej, J.; Kania, R.S. Molecular conformations, interactions, and properties associated with drug efficiency and clinical performance among VEGFR TK inhibitors. Proc. Natl. Acad. Sci. USA, 2012, 109(45), 18281-18289.
[http://dx.doi.org/10.1073/pnas.1207759109] [PMID: 22988103]
[46]
Hennequin, L.F.; Thomas, A.P.; Johnstone, C.; Stokes, E.S.E.; Plé, P.A.; Lohmann, J-J.M.; Ogilvie, D.J.; Dukes, M.; Wedge, S.R.; Curwen, J.O.; Kendrew, J.; Lambert-van der Brempt, C. Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J. Med. Chem., 1999, 42(26), 5369-5389.
[http://dx.doi.org/10.1021/jm990345w] [PMID: 10639280]
[47]
Hennequin, L.F.; Stokes, E.S.E.; Thomas, A.P.; Johnstone, C.; Plé, P.A.; Ogilvie, D.J.; Dukes, M.; Wedge, S.R.; Kendrew, J.; Curwen, J.O. Novel 4-anilinoquinazolines with C-7 basic side chains: Design and structure activity relationship of a series of potent, orally active, VEGF receptor tyrosine kinase inhibitors. J. Med. Chem., 2002, 45(6), 1300-1312.
[http://dx.doi.org/10.1021/jm011022e] [PMID: 11881999]
[48]
Cui, J.J.; Tran-Dubé, M.; Shen, H.; Nambu, M.; Kung, P-P.; Pairish, M.; Jia, L.; Meng, J.; Funk, L.; Botrous, I.; McTigue, M.; Grodsky, N.; Ryan, K.; Padrique, E.; Alton, G.; Timofeevski, S.; Yamazaki, S.; Li, Q.; Zou, H.; Christensen, J.; Mroczkowski, B.; Bender, S.; Kania, R.S.; Edwards, M.P. Structure based drug design of crizotinib (PF-02341066), a potent and selective dual inhibitor of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic lymphoma kinase (ALK). J. Med. Chem., 2011, 54(18), 6342-6363.
[http://dx.doi.org/10.1021/jm2007613] [PMID: 21812414]
[49]
Johnson, T.R.; Tan, W.; Goulet, L.; Smith, E.B.; Yamazaki, S.; Walker, G.S.; O’Gorman, M.T.; Bedarida, G.; Zou, H.Y.; Christensen, J.G.; Nguyen, L.N.; Shen, Z.; Dalvie, D.; Bello, A.; Smith, B.J. Metabolism, excretion and pharmacokinetics of [14C]crizotinib following oral administration to healthy subjects. Xenobiotica, 2015, 45(1), 45-59.
[http://dx.doi.org/10.3109/00498254.2014.941964] [PMID: 25034009]
[50]
Dorsch, D.; Schadt, O.; Stieber, F.; Meyring, M.; Grädler, U.; Bladt, F.; Friese-Hamim, M.; Knühl, C.; Pehl, U.; Blaukat, A. Identification and optimization of pyridazinones as potent and selective c-Met kinase inhibitors. Bioorg. Med. Chem. Lett., 2015, 25(7), 1597-1602.
[http://dx.doi.org/10.1016/j.bmcl.2015.02.002] [PMID: 25736998]
[51]
Johne, A.; Scheible, H.; Becker, A.; van Lier, J.J.; Wolna, P.; Meyring, M. Open-label, single-center, phase I trial to investigate the mass balance and absolute bioavailability of the highly selective oral MET inhibitor tepotinib in healthy volunteers. Invest. New Drugs, 2020, 38(5), 1507-1519.
[http://dx.doi.org/10.1007/s10637-020-00926-1] [PMID: 32221754]
[52]
Galkin, A.V.; Melnick, J.S.; Kim, S.; Hood, T.L.; Li, N.; Li, L.; Xia, G.; Steensma, R.; Chopiuk, G.; Jiang, J.; Wan, Y.; Ding, P.; Liu, Y.; Sun, F.; Schultz, P.G.; Gray, N.S.; Warmuth, M. Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK. Proc. Natl. Acad. Sci. USA, 2007, 104(1), 270-275.
[http://dx.doi.org/10.1073/pnas.0609412103] [PMID: 17185414]
[53]
Marsilje, T.H.; Pei, W.; Chen, B.; Lu, W.; Uno, T.; Jin, Y.; Jiang, T.; Kim, S.; Li, N.; Warmuth, M.; Sarkisova, Y.; Sun, F.; Steffy, A.; Pferdekamper, A.C.; Li, A.G.; Joseph, S.B.; Kim, Y.; Liu, B.; Tuntland, T.; Cui, X.; Gray, N.S.; Steensma, R.; Wan, Y.; Jiang, J.; Chopiuk, G.; Li, J.; Gordon, W.P.; Richmond, W.; Johnson, K.; Chang, J.; Groessl, T.; He, Y-Q.; Phimister, A.; Aycinena, A.; Lee, C.C.; Bursulaya, B.; Karanewsky, D.S.; Seidel, H.M.; Harris, J.L.; Michellys, P-Y. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(iso-propylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J. Med. Chem., 2013, 56(14), 5675-5690.
[http://dx.doi.org/10.1021/jm400402q] [PMID: 23742252]
[54]
Kinoshita, K.; Kobayashi, T.; Asoh, K.; Furuichi, N.; Ito, T.; Kawada, H.; Hara, S.; Ohwada, J.; Hattori, K.; Miyagi, T.; Hong, W-S.; Park, M-J.; Takanashi, K.; Tsukaguchi, T.; Sakamoto, H.; Tsukuda, T.; Oikawa, N. 9-substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles as highly selective and potent anaplastic lymphoma kinase inhibitors. J. Med. Chem., 2011, 54(18), 6286-6294.
[http://dx.doi.org/10.1021/jm200652u] [PMID: 21823617]
[55]
Kinoshita, K.; Ono, Y.; Emura, T.; Asoh, K.; Furuichi, N.; Ito, T.; Kawada, H.; Tanaka, S.; Morikami, K.; Tsukaguchi, T.; Sakamoto, H.; Tsukuda, T.; Oikawa, N. Discovery of novel tetracyclic compounds as anaplastic lymphoma kinase inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(12), 3788-3793.
[http://dx.doi.org/10.1016/j.bmcl.2011.04.020] [PMID: 21561771]
[56]
Kinoshita, K.; Asoh, K.; Furuichi, N.; Ito, T.; Kawada, H.; Hara, S.; Ohwada, J.; Miyagi, T.; Kobayashi, T.; Takanashi, K.; Tsukaguchi, T.; Sakamoto, H.; Tsukuda, T.; Oikawa, N. Design and synthesis of a highly selective, orally active and potent anaplastic lymphoma kinase inhibitor (CH5424802). Bioorg. Med. Chem., 2012, 20(3), 1271-1280.
[http://dx.doi.org/10.1016/j.bmc.2011.12.021] [PMID: 22225917]
[57]
Huang, W-S.; Liu, S.; Zou, D.; Thomas, M.; Wang, Y.; Zhou, T.; Romero, J.; Kohlmann, A.; Li, F.; Qi, J.; Cai, L.; Dwight, T.A.; Xu, Y.; Xu, R.; Dodd, R.; Toms, A.; Parillon, L.; Lu, X.; Anjum, R.; Zhang, S.; Wang, F.; Keats, J.; Wardwell, S.D.; Ning, Y.; Xu, Q.; Moran, L.E.; Mohemmad, Q.K.; Jang, H.G.; Clackson, T.; Narasimhan, N.I.; Rivera, V.M.; Zhu, X.; Dalgarno, D.; Shakespeare, W.C. Discovery of brigatinib (AP26113), a phosphine oxide-containing, potent, orally active inhibitor of anaplastic lymphoma kinase. J. Med. Chem., 2016, 59(10), 4948-4964.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00306] [PMID: 27144831]
[58]
Kadi, A.A.; Attwa, M.W.; Darwish, H.W. LC-ESI-MS/MS reveals the formation of reactive intermediates in brigatinib metabolism: Elucidation of bioactivation pathways. RSC Advances, 2018, 8(3), 1182-1190.
[http://dx.doi.org/10.1039/C7RA10533A] [PMID: 35540908]
[59]
Menichincheri, M.; Ardini, E.; Magnaghi, P.; Avanzi, N.; Banfi, P.; Bossi, R.; Buffa, L.; Canevari, G.; Ceriani, L.; Colombo, M.; Corti, L.; Donati, D.; Fasolini, M.; Felder, E.; Fiorelli, C.; Fiorentini, F.; Galvani, A.; Isacchi, A.; Borgia, A.L.; Marchionni, C.; Nesi, M.; Orrenius, C.; Panzeri, A.; Pesenti, E.; Rusconi, L.; Saccardo, M.B.; Vanotti, E.; Perrone, E.; Orsini, P. Discovery of entrectinib: A new 3-aminoindazole as a potent anaplastic lymphoma kinase (ALK), c-Ros oncogene 1 kinase (ROS1), and pan-tropomyosin receptor kinases (pan-TRKs) inhibitor. J. Med. Chem., 2016, 59(7), 3392-3408.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00064] [PMID: 27003761]
[60]
Attwa, M.W.; Kadi, A.A.; Alrabiah, H.; Darwish, H.W. LC-MS/MS reveals the formation of iminium and quinone methide reactive intermediates in entrectinib metabolism: In vivo and in vitro metabolic investigation. J. Pharm. Biomed. Anal., 2018, 160, 19-30.
[http://dx.doi.org/10.1016/j.jpba.2018.07.032] [PMID: 30055343]
[61]
Huang, Q.; Johnson, T.W.; Bailey, S.; Brooun, A.; Bunker, K.D.; Burke, B.J.; Collins, M.R.; Cook, A.S.; Cui, J.J.; Dack, K.N.; Deal, J.G.; Deng, Y-L.; Dinh, D.; Engstrom, L.D.; He, M.; Hoffman, J.; Hoffman, R.L.; Johnson, P.S.; Kania, R.S.; Lam, H.; Lam, J.L.; Le, P.T.; Li, Q.; Lingardo, L.; Liu, W.; Lu, M.W.; McTigue, M.; Palmer, C.L.; Richardson, P.F.; Sach, N.W.; Shen, H.; Smeal, T.; Smith, G.L.; Stewart, A.E.; Timofeevski, S.; Tsaparikos, K.; Wang, H.; Zhu, H.; Zhu, J.; Zou, H.Y.; Edwards, M.P. Design of potent and selective inhibitors to overcome clinical anaplastic lymphoma kinase mutations resistant to crizotinib. J. Med. Chem., 2014, 57(4), 1170-1187.
[http://dx.doi.org/10.1021/jm401805h] [PMID: 24432909]
[62]
Johnson, T.W.; Richardson, P.F.; Bailey, S.; Brooun, A.; Burke, B.J.; Collins, M.R.; Cui, J.J.; Deal, J.G.; Deng, Y-L.; Dinh, D.; Engstrom, L.D.; He, M.; Hoffman, J.; Hoffman, R.L.; Huang, Q.; Kania, R.S.; Kath, J.C.; Lam, H.; Lam, J.L.; Le, P.T.; Lingardo, L.; Liu, W.; McTigue, M.; Palmer, C.L.; Sach, N.W.; Smeal, T.; Smith, G.L.; Stewart, A.E.; Timofeevski, S.; Zhu, H.; Zhu, J.; Zou, H.Y.; Edwards, M.P. Discovery of (10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno) pyrazolo[4,3-h][2,5,11]-benzoxadiazacyclotetradecine-3-carbonitrile (PF-06463922), a macrocyclic inhibitor of anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) with preclinical brain exposure and broad-spectrum potency against ALK-resistant mutations. J. Med. Chem., 2014, 57(11), 4720-4744.
[http://dx.doi.org/10.1021/jm500261q] [PMID: 24819116]
[63]
Nakajima, Y.; Tojo, T.; Morita, M.; Hatanaka, K.; Shirakami, S.; Tanaka, A.; Sasaki, H.; Nakai, K.; Mukoyoshi, K.; Hamaguchi, H.; Takahashi, F.; Moritomo, A.; Higashi, Y.; Inoue, T. Synthesis and evaluation of 1H-pyrrolo[2,3-b]pyridine derivatives as novel immunomodulators targeting janus kinase 3. Chem. Pharm. Bull. (Tokyo), 2015, 63(5), 341-353.
[http://dx.doi.org/10.1248/cpb.c15-00036] [PMID: 25786493]
[64]
Hamaguchi, H.; Amano, Y.; Moritomo, A.; Shirakami, S.; Nakajima, Y.; Nakai, K.; Nomura, N.; Ito, M.; Higashi, Y.; Inoue, T. Discovery and structural characterization of peficitinib (ASP015K) as a novel and potent JAK inhibitor. Bioorg. Med. Chem., 2018, 26(18), 4971-4983.
[http://dx.doi.org/10.1016/j.bmc.2018.08.005] [PMID: 30145050]
[65]
Noji, S.; Hara, Y.; Miura, T.; Yamanaka, H.; Maeda, K.; Hori, A.; Yamamoto, H.; Obika, S.; Inoue, M.; Hase, Y.; Orita, T.; Doi, S.; Adachi, T.; Tanimoto, A.; Oki, C.; Kimoto, Y.; Ogawa, Y.; Negoro, T.; Hashimoto, H.; Shiozaki, M. Discovery of a Janus kinase inhibitor bearing a highly three-dimensional spiro scaffold: JTE-052 (delgocitinib) as a new dermatological agent to treat inflammatory skin disorders. J. Med. Chem., 2020, 63(13), 7163-7185.
[http://dx.doi.org/10.1021/acs.jmedchem.0c00450] [PMID: 32511913]
[66]
Menet, C.J.; Fletcher, S.R.; Van Lommen, G.; Geney, R.; Blanc, J.; Smits, K.; Jouannigot, N.; Deprez, P.; van der Aar, E.M.; Clement-Lacroix, P.; Lepescheux, L.; Galien, R.; Vayssiere, B.; Nelles, L.; Christophe, T.; Brys, R.; Uhring, M.; Ciesielski, F.; Van Rompaey, L. Triazolopyridines as selective JAK1 inhibitors: From hit identification to GLPG0634. J. Med. Chem., 2014, 57(22), 9323-9342.
[http://dx.doi.org/10.1021/jm501262q] [PMID: 25369270]
[67]
Van Rompaey, L.; Galien, R.; van der Aar, E.M.; Clement-Lacroix, P.; Nelles, L.; Smets, B.; Lepescheux, L.; Christophe, T.; Conrath, K.; Vandeghinste, N.; Vayssiere, B.; De Vos, S.; Fletcher, S.; Brys, R.; van ’t Klooster, G.; Feyen, J.H.M.; Menet, C. Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J. Immunol., 2013, 191(7), 3568-3577.
[http://dx.doi.org/10.4049/jimmunol.1201348] [PMID: 24006460]
[68]
Vazquez, M.L.; Kaila, N.; Strohbach, J.W.; Trzupek, J.D.; Brown, M.F.; Flanagan, M.E.; Mitton-Fry, M.J.; Johnson, T.A.; TenBrink, R.E.; Arnold, E.P.; Basak, A.; Heasley, S.E.; Kwon, S.; Langille, J.; Parikh, M.D.; Griffin, S.H.; Casavant, J.M.; Duclos, B.A.; Fenwick, A.E.; Harris, T.M.; Han, S.; Caspers, N.; Dowty, M.E.; Yang, X.; Banker, M.E.; Hegen, M.; Symanowicz, P.T.; Li, L.; Wang, L.; Lin, T.H.; Jussif, J.; Clark, J.D.; Telliez, J-B.; Robinson, R.P.; Unwalla, R. Identification of N-cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutylpropane-1-sulfonamide (PF-04965842): A selective JAK1 clinical candidate for the treatment of autoimmune diseases. J. Med. Chem., 2018, 61(3), 1130-1152.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01598] [PMID: 29298069]
[69]
Tripathy, S.; Wentzel, D.; Wan, X.K.; Kavetska, O. Validation of enantioseparation and quantitation of an active metabolite of abrocitinib in human plasma. Bioanalysis, 2021, 13(19), 1477-1486.
[http://dx.doi.org/10.4155/bio-2021-0128] [PMID: 34601943]
[70]
Wang, E.Q.; Le, V.; O’Gorman, M.; Tripathy, S.; Dowty, M.E.; Wang, L.; Malhotra, B.K. Effects of hepatic impairment on the pharmacokinetics of abrocitinib and its metabolites. J. Clin. Pharmacol., 2021, 61(10), 1311-1323.
[http://dx.doi.org/10.1002/jcph.1858] [PMID: 33749838]
[71]
Patel, H.K.; Grotzfeld, R.M.; Lai, A.G.; Mehta, S.A.; Milanov, Z.V.; Chao, Q.; Sprankle, K.G.; Carter, T.A.; Velasco, A.M.; Fabian, M.A.; James, J.; Treiber, D.K.; Lockhart, D.J.; Zarrinkar, P.P.; Bhagwat, S.S. Arylcarboxyamino-substituted diaryl ureas as potent and selective FLT3 inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(17), 5182-5185.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.024] [PMID: 19646870]
[72]
Chao, Q.; Sprankle, K.G.; Grotzfeld, R.M.; Lai, A.G.; Carter, T.A.; Velasco, A.M.; Gunawardane, R.N.; Cramer, M.D.; Gardner, M.F.; James, J.; Zarrinkar, P.P.; Patel, H.K.; Bhagwat, S.S. Identification of N-(5-tert-butyl-isoxazol-3-yl)-N′-{4-[7-(2-morpholin-4-yl-ethoxy)imidazo[2,1-b][1,3] benzothiazol-2-yl]phenyl}urea dihydrochloride (AC220), a uniquely potent, selective, and efficacious FMS-like tyrosine kinase-3 (FLT3). Inhibitor. J. Med. Chem., 2009, 52(23), 7808-7816.
[http://dx.doi.org/10.1021/jm9007533] [PMID: 19754199]
[73]
Zorn, J.A.; Wang, Q.; Fujimura, E.; Barros, T.; Kuriyan, J. Crystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220). PLoS One, 2015, 10(4), e0121177.
[http://dx.doi.org/10.1371/journal.pone.0121177] [PMID: 25837374]
[74]
Wu, L.; Zhang, C.; He, C.; Qian, D.; Lu, L.; Sun, Y.; Xu, M.; Zhuo, J.; Liu, P.C.C.; Klabe, R.; Wynn, R.; Covington, M.; Gallagher, K.; Leffet, L.; Bowman, K.; Diamond, S.; Koblish, H.; Zhang, Y.; Soloviev, M.; Hollis, G.; Burn, T.C.; Scherle, P.; Yeleswaram, S.; Huber, R.; Yao, W. Discovery of pemigatinib: A potent and selective fibroblast growth factor receptor (FGFR) inhibitor. J. Med. Chem., 2021, 64(15), 10666-10679.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00713] [PMID: 34269576]
[75]
Ji, T.; Rockich, K.; Epstein, N.; Overholt, H.; Wang, P.; Chen, X.; Punwani, N.; Yeleswaram, S. Evaluation of drug-drug interactions of pemigatinib in healthy participants. Eur. J. Clin. Pharmacol., 2021, 77(12), 1887-1897.
[http://dx.doi.org/10.1007/s00228-021-03184-z] [PMID: 34282472]
[76]
Guagnano, V.; Furet, P.; Spanka, C.; Bordas, V.; Le Douget, M.; Stamm, C.; Brueggen, J.; Jensen, M.R.; Schnell, C.; Schmid, H.; Wartmann, M.; Berghausen, J.; Drueckes, P.; Zimmerlin, A.; Bussiere, D.; Murray, J.; Graus Porta, D. Discovery of 3-(2,6-dichloro-3,5-dime-thoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylami-no]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase. J. Med. Chem., 2011, 54(20), 7066-7083.
[http://dx.doi.org/10.1021/jm2006222] [PMID: 21936542]
[77]
Tang, L.W.T.; Teng, J.W.; Verma, R.K.; Koh, S.K.; Zhou, L.; Go, M.L.; Fan, H.; Chan, E.C.Y. Infigratinib is a reversible inhibitor and mechanism-based inactivator of cytochrome P450 3A4. Drug Metab. Dispos., 2021, 49(9), 856-868.
[http://dx.doi.org/10.1124/dmd.121.000508] [PMID: 34326139]
[78]
Lombardo, L.J.; Lee, F.Y.; Chen, P.; Norris, D.; Barrish, J.C.; Behnia, K.; Castaneda, S.; Cornelius, L.A.M.; Das, J.; Doweyko, A.M.; Fairchild, C.; Hunt, J.T.; Inigo, I.; Johnston, K.; Kamath, A.; Kan, D.; Klei, H.; Marathe, P.; Pang, S.; Peterson, R.; Pitt, S.; Schieven, G.L.; Schmidt, R.J.; Tokarski, J.; Wen, M-L.; Wityak, J.; Borzilleri, R.M. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydro-xyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino) thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J. Med. Chem., 2004, 47(27), 6658-6661.
[http://dx.doi.org/10.1021/jm049486a] [PMID: 15615512]
[79]
Tokarski, J.S.; Newitt, J.A.; Chang, C.Y.J.; Cheng, J.D.; Wittekind, M.; Kiefer, S.E.; Kish, K.; Lee, F.Y.F.; Borzillerri, R.; Lombardo, L.J.; Xie, D.; Zhang, Y.; Klei, H.E. The structure of dasatinib (BMS-354825) bound to activated ABL kinase domain elucidates its inhibitory activity against imatinib-resistant ABL mutants. Cancer Res., 2006, 66(11), 5790-5797.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4187] [PMID: 16740718]
[80]
Boschelli, D.H.; Ye, F.; Wang, Y.D.; Dutia, M.; Johnson, S.L.; Wu, B.; Miller, K.; Powell, D.W.; Yaczko, D.; Young, M.; Tischler, M.; Arndt, K.; Discafani, C.; Etienne, C.; Gibbons, J.; Grod, J.; Lucas, J.; Weber, J.M.; Boschelli, F. Optimization of 4-phenylamino-3-quinolinecarbonitriles as potent inhibitors of Src kinase activity. J. Med. Chem., 2001, 44(23), 3965-3977.
[http://dx.doi.org/10.1021/jm0102250] [PMID: 11689083]
[81]
Golas, J.M.; Arndt, K.; Etienne, C.; Lucas, J.; Nardin, D.; Gibbons, J.; Frost, P.; Ye, F.; Boschelli, D.H.; Boschelli, F. SKI-606, a 4-anilino-3-quinolinecarbonitrile dual inhibitor of Src and Abl kinases, is a potent antiproliferative agent against chronic myelogenous leukemia cells in culture and causes regression of K562 xenografts in nude mice. Cancer Res., 2003, 63(2), 375-381. Available from: https://aacrjournals.org/cancerres/article/63/2/375/510517
[PMID: 12543790]
[82]
Boschelli, D.H.; Wang, Y.D.; Johnson, S.; Wu, B.; Ye, F.; Barrios Sosa, A.C.; Golas, J.M.; Boschelli, F. 7-Alkoxy-4-phenylamino-3-quinolinecar-bonitriles as dual inhibitors of Src and Abl kinases. J. Med. Chem., 2004, 47(7), 1599-1601.
[http://dx.doi.org/10.1021/jm0499458] [PMID: 15027848]
[83]
Levinson, N.M.; Boxer, S.G. Structural and spectroscopic analysis of the kinase inhibitor bosutinib and an isomer of bosutinib binding to the Abl tyrosine kinase domain. PLoS One, 2012, 7(4), e29828.
[http://dx.doi.org/10.1371/journal.pone.0029828] [PMID: 22493660]
[84]
Levinson, N.M.; Boxer, S.G. A conserved water-mediated hydrogen bond network defines Bosutinib’s kinase selectivity. Nat. Chem. Biol., 2014, 10(2), 127-132.
[http://dx.doi.org/10.1038/nchembio.1404] [PMID: 24292070]
[85]
Huang, W-S.; Metcalf, C.A.; Sundaramoorthi, R.; Wang, Y.; Zou, D.; Thomas, R.M.; Zhu, X.; Cai, L.; Wen, D.; Liu, S.; Romero, J.; Qi, J.; Chen, I.; Banda, G.; Lentini, S.P.; Das, S.; Xu, Q.; Keats, J.; Wang, F.; Wardwell, S.; Ning, Y.; Snodgrass, J.T.; Broudy, M.I.; Russian, K.; Zhou, T.; Commodore, L.; Narasimhan, N.I.; Mohemmad, Q.K.; Iuliucci, J.; Rivera, V.M.; Dalgarno, D.C.; Sawyer, T.K.; Clackson, T.; Shakespeare, W.C. Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenylbenzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. J. Med. Chem., 2010, 53(12), 4701-4719.
[http://dx.doi.org/10.1021/jm100395q] [PMID: 20513156]
[86]
O’Hare, T.; Shakespeare, W.C.; Zhu, X.; Eide, C.A.; Rivera, V.M.; Wang, F.; Adrian, L.T.; Zhou, T.; Huang, W-S.; Xu, Q.; Metcalf, C.A., III; Tyner, J.W.; Loriaux, M.M.; Corbin, A.S.; Wardwell, S.; Ning, Y.; Keats, J.A.; Wang, Y.; Sundaramoorthi, R.; Thomas, M.; Zhou, D.; Snodgrass, J.; Commodore, L.; Sawyer, T.K.; Dalgarno, D.C.; Deininger, M.W.N.; Druker, B.J.; Clackson, T. AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance. Cancer Cell, 2009, 16(5), 401-412.
[http://dx.doi.org/10.1016/j.ccr.2009.09.028] [PMID: 19878872]
[87]
Ye, Y.E.; Woodward, C.N.; Narasimhan, N.I. Absorption, metabolism, and excretion of [14C]ponatinib after a single oral dose in humans. Cancer Chemother. Pharmacol., 2017, 79(3), 507-518.
[http://dx.doi.org/10.1007/s00280-017-3240-x] [PMID: 28184964]
[88]
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]
[89]
Hughes, T.P.; Mauro, M.J.; Cortes, J.E.; Minami, H.; Rea, D.; DeAngelo, D.J.; Breccia, M.; Goh, Y-T.; Talpaz, M.; Hochhaus, A.; le Coutre, P.; Ottmann, O.; Heinrich, M.C.; Steegmann, J.L.; Deininger, M.W.N.; Janssen, J.J.W.M.; Mahon, F-X.; Minami, Y.; Yeung, D.; Ross, D.M.; Tallman, M.S.; Park, J.H.; Druker, B.J.; Hynds, D.; Duan, Y.; Meille, C.; Hourcade-Potelleret, F.; Vanasse, K.G.; Lang, F.; Kim, D-W. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N. Engl. J. Med., 2019, 381(24), 2315-2326.
[http://dx.doi.org/10.1056/NEJMoa1902328] [PMID: 31826340]
[90]
Abe, H.; Kikuchi, S.; Hayakawa, K.; Iida, T.; Nagahashi, N.; Maeda, K.; Sakamoto, J.; Matsumoto, N.; Miura, T.; Matsumura, K.; Seki, N.; Inaba, T.; Kawasaki, H.; Yamaguchi, T.; Kakefuda, R.; Nanayama, T.; Kurachi, H.; Hori, Y.; Yoshida, T.; Kakegawa, J.; Watanabe, Y.; Gilmartin, A.G.; Richter, M.C.; Moss, K.G.; Laquerre, S.G. Discovery of a highly potent and selective MEK inhibitor: GSK1120212 (JTP-74057 DMSO solvate). ACS Med. Chem. Lett., 2011, 2(4), 320-324.
[http://dx.doi.org/10.1021/ml200004g] [PMID: 24900312]
[91]
Gonzalez-Del Pino, G.L.; Li, K.; Park, E.; Schmoker, A.M.; Ha, B.H.; Eck, M.J. Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation. Proc. Natl. Acad. Sci. USA, 2021, 118(36), e2107207118.
[http://dx.doi.org/10.1073/pnas.2107207118] [PMID: 34470822]
[92]
Rice, K.D.; Aay, N.; Anand, N.K.; Blazey, C.M.; Bowles, O.J.; Bussenius, J.; Costanzo, S.; Curtis, J.K.; Defina, S.C.; Dubenko, L.; Engst, S.; Joshi, A.A.; Kennedy, A.R.; Kim, A.I.; Koltun, E.S.; Lougheed, J.C.; Manalo, J-C.L.; Martini, J-F.; Nuss, J.M.; Peto, C.J.; Tsang, T.H.; Yu, P.; Johnston, S. Novel carboxamide-based allosteric MEK inhibitors: Discovery and optimization efforts toward XL518 (GDC-0973). ACS Med. Chem. Lett., 2012, 3(5), 416-421.
[http://dx.doi.org/10.1021/ml300049d] [PMID: 24900486]
[93]
Takahashi, R.H.; Ma, S.; Yue, Q.; Kim-Kang, H.; Yi, Y.; Ly, J.; Boggs, J.W.; Fettes, A.; McClory, A.; Deng, Y.; Hop, C.E.C.A.; Khojasteh, S.C.; Choo, E.F. Absorption, metabolism and excretion of cobimetinib, an oral MEK inhibitor, in rats and dogs. Xenobiotica, 2017, 47(1), 50-65.
[http://dx.doi.org/10.3109/00498254.2016.1157645] [PMID: 27055783]
[94]
Takahashi, R.H.; Choo, E.F.; Ma, S.; Wong, S.; Halladay, J.; Deng, Y.; Rooney, I.; Gates, M.; Hop, C.E.C.A.; Khojasteh, S.C.; Dresser, M.J.; Musib, L. Absorption, metabolism, excretion, and the contribution of intestinal metabolism to the oral disposition of [14C]cobimetinib, a MEK inhibitor, in humans. Drug Metab. Dispos., 2016, 44(1), 28-39.
[http://dx.doi.org/10.1124/dmd.115.066282] [PMID: 26451002]
[95]
Guo, Y.; Liu, Y.; Hu, N.; Yu, D.; Zhou, C.; Shi, G.; Zhang, B.; Wei, M.; Liu, J.; Luo, L.; Tang, Z.; Song, H.; Guo, Y.; Liu, X.; Su, D.; Zhang, S.; Song, X.; Zhou, X.; Hong, Y.; Chen, S.; Cheng, Z.; Young, S.; Wei, Q.; Wang, H.; Wang, Q.; Lv, L.; Wang, F.; Xu, H.; Sun, H.; Xing, H.; Li, N.; Zhang, W.; Wang, Z.; Liu, G.; Sun, Z.; Zhou, D.; Li, W.; Liu, L.; Wang, L.; Wang, Z. Discovery of zanubrutinib (BGB-3111), a novel, potent, and selective covalent inhibitor of bruton’s tyrosine kinase. J. Med. Chem., 2019, 62(17), 7923-7940.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00687] [PMID: 31381333]
[96]
Zhang, H.; Ou, Y.C.; Su, D.; Wang, F.; Wang, L.; Sahasranaman, S.; Tang, Z. in vitro investigations into the roles of CYP450 enzymes and drug transporters in the drug interactions of zanubrutinib, a covalent Bruton’s tyrosine kinase inhibitor. Pharmacol. Res. Perspect., 2021, 9(6), e00870.
[http://dx.doi.org/10.1002/prp2.870] [PMID: 34664792]
[97]
Mori, M.; Kaneko, N.; Ueno, Y.; Yamada, M.; Tanaka, R.; Saito, R.; Shimada, I.; Mori, K.; Kuromitsu, S. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest. New Drugs, 2017, 35(5), 556-565.
[http://dx.doi.org/10.1007/s10637-017-0470-z] [PMID: 28516360]
[98]
Kawase, T.; Nakazawa, T.; Eguchi, T.; Tsuzuki, H.; Ueno, Y.; Amano, Y.; Suzuki, T.; Mori, M.; Yoshida, T. Effect of Fms-like tyrosine kinase 3 (FLT3) ligand (FL) on antitumor activity of gilteritinib, a FLT3 inhibitor, in mice xenografted with FL-overexpressing cells. Oncotarget, 2019, 10(58), 6111-6123.
[http://dx.doi.org/10.18632/oncotarget.27222] [PMID: 31692922]
[99]
Roth, G.J.; Heckel, A.; Colbatzky, F.; Handschuh, S.; Kley, J.; Lehmann-Lintz, T.; Lotz, R.; Tontsch-Grunt, U.; Walter, R.; Hilberg, F. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J. Med. Chem., 2009, 52(14), 4466-4480.
[http://dx.doi.org/10.1021/jm900431g] [PMID: 19522465]
[100]
Hilberg, F.; Roth, G.J.; Krssak, M.; Kautschitsch, S.; Sommergruber, W.; Tontsch-Grunt, U.; Garin-Chesa, P.; Bader, G.; Zoephel, A.; Quant, J.; Heckel, A.; Rettig, W.J. BIBF 1120: Triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res., 2008, 68(12), 4774-4782.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6307] [PMID: 18559524]
[101]
Zimmermann, J.; Buchdunger, E.; Mett, H.; Meyer, T.; Lydon, N.B. Potent and selective inhibitors of the Abl-kinase: Phenylamino-pyrimidine (PAP) derivatives. Bioorg. Med. Chem. Lett., 1997, 7(2), 187-192.
[http://dx.doi.org/10.1016/S0960-894X(96)00601-4]
[102]
Nagar, B.; Bornmann, W.G.; Pellicena, P.; Schindler, T.; Veach, D.R.; Miller, W.T.; Clarkson, B.; Kuriyan, J. Crystal structures of the kinase domain of c-Abl in complex with the small molecule inhibitors PD173955 and imatinib (STI-571). Cancer Res., 2002, 62(15), 4236-4243.https://aacrjournals.org/cancerres/article/62/15/4236/509099
[PMID: 12154025]
[103]
Gelbert, L.M.; Cai, S.; Lin, X.; Sanchez-Martinez, C.; Del Prado, M.; Lallena, M.J.; Torres, R.; Ajamie, R.T.; Wishart, G.N.; Flack, R.S.; Neubauer, B.L.; Young, J.; Chan, E.M.; Iversen, P.; Cronier, D.; Kreklau, E.; de Dios, A. Preclinical characterization of the CDK4/6 inhibitor LY2835219: In-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest. New Drugs, 2014, 32(5), 825-837.
[http://dx.doi.org/10.1007/s10637-014-0120-7] [PMID: 24919854]
[104]
Bronner, S.M.; Merrick, K.A.; Murray, J.; Salphati, L.; Moffat, J.G.; Pang, J.; Sneeringer, C.J.; Dompe, N.; Cyr, P.; Purkey, H.; Boenig, G.L.; Li, J.; Kolesnikov, A.; Larouche-Gauthier, R.; Lai, K.W.; Shen, X.; Aubert-Nicol, S.; Chen, Y-C.; Cheong, J.; Crawford, J.J.; Hafner, M.; Haghshenas, P.; Jakalian, A.; Leclerc, J-P.; Lim, N-K.; O’Brien, T.; Plise, E.G.; Shalan, H.; Sturino, C.; Wai, J.; Xiao, Y.; Yin, J.; Zhao, L.; Gould, S.; Olivero, A.; Heffron, T.P. Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma. Bioorg. Med. Chem. Lett., 2019, 29(16), 2294-2301.
[http://dx.doi.org/10.1016/j.bmcl.2019.06.021] [PMID: 31307887]

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