Molecules Engineered Against Oncogenic Proteins and Cancer: Discovery, Design, and Development

ISBN-13: 9781394207084 / Twarda / 2023 / 400 str.

Corey

Spis treści

Preface viiChapter 1. Introduction 11.1 Types of Protein Kinases 11.2 Protein Kinase Domains 11.3 ATP-Binding Site 21.4 Types of Kinase Inhibitors 31.5 Brief History of Smallmolecule Kinase Inhibitors 51.6 Peak 12-Month Sales for Leading Kinase Inhibitors 71.7 Approved Kinase Inhibitors 7Chapter 2. BCR-ABL Inhibitors 182.1 Imatinib* (1) 192.2 Nilotinib* (2) 242.3 Dasatinib* (3) 272.4 Bosutinib* (4) 302.5 Ponatinib* (5) 332.6 Olvermbatinib** (6) 372.7 Asciminib* (7) 38Chapter 3. BTK Inhibitors 433.1 Ibrutinib* (8) 453.2 Acalabrutinib* (9) 513.3 Zanubrutinib* (10) 543.4 Tirabrutinib** (11) 573.5 Orelabrutinib** (12) 58Chapter 4. EGFR/HER Family Inhibitors 594.1 Gefitinib* (13) 614.2 Erlotinib * (14) 674.3 Icotinib** (15) 724.4 Afatinib* (16) 744.5 Dacomitinib* (17) 774.6 Osimertinib* (18) 804.7 Mobocertinib* (19) 864.8 Lapatinib* (20) 904.9 Tucatinib* (21) 934.10 Neratinib* (22) 95Chapter 5. VEGFR/Multikinase Inhibitors 975.1 Sorafenib* (23) 995.2 Regorafenib* (24) 1045.3 Sunitinib* (25) 1065.4 Pazopanib* (26) 1125.5 Axitinib* (27) 1145.6 Nintedanib* (28) 1175.7 Apatinib** (29) 1215.8 Lenvatinib* (30) 1225.9 Tovozanib* (31) 125Chapter 6. CDK4/6 Inhibitors 1276.1 Palbociclib* (32) 1296.2 Ribociclib*(33) 1366.3 Abemaciclib* (34) 1396.4 Trilaciclib* (35) 142Chapter 7. JAK Inhibitors 1447.1 Tofacitinib* (36) 1477.2 Baricitinib* (37) 1517.3 Peficitinib** (38) 1537.4 Upadacitinib* (39) 1587.5 Delgocitinib** (40) 1617.6 Filgotinib** (41) 1637.7 Abrocitinib* (42) 1667.8 Ruxolitinib* (43) 1707.9 Fedratinib* (44) 1737.10 Pacritinib* (45) 1757.11 Ritlecitinib # (46) 1777.12 Brepocitinib # (47) 1817.13 Ropsacitinib # (48) 184Chapter 8. Allosteric TYK2 Inhibitors 1878.1 Deucravacitinib* (49) 189Chapter 9. ALK/multikinase Inhibitors 1959.1 Crizotinib* (50) 1979.2 Ceritinib* (51) 2029.3 Alectinib* (52) 2059.4 Brigatinib* (53) 2079.5 Lorlatinib* (54) 210Chapter 10. BRAF/Multikinase Inhibitors 21410.1 Vemurafenib* (55) 21610.2 Dabrafenib* (56) 22210.3 Encorafenib* (57) 225Chapter 11. MEK Inhibitors 22711.1 Trametinib* (58) 22811.2 Cobimetinib* (59) 23211.3 Binimetinib* (60) 23511.4 Selumetinib* (61) 237Chapter 12. RET/Multikinase Inhibitors 24012.1 Vandetanib* (62) 24212.2 Cabozantinib* (63) 24512.3 Selpercatinib* (64) 24712.4 Pralsetinib* (65) 251Chapter 13. FGFR Inhibitors 25313.1 Erdafitinib* (66) 25513.2 Pemigatinib* (67) 26013.3 Infigratinib* (68) 26313.4 Futibatinib* (69) 265Chapter 14. PI3K Inhibitors 26714.1 Alpelisib* (70) 26914.2 Idelalisib* (71) 27314.3 Duvelisib* (72) 27714.4 Umbralisib* (73) 27914.5 Copanlisib* (74) 281Chapter 15. TRK/Multikinase Inhibitors 28415.1 Larotrectinib* (75) 28515.2 Entrectinib* (76) 28815.3 Repotrectinib # (77) 291Chapter 16. MET Inhibitors 29416.1 Capmatinib* (78) 29516.2 Tepotinib* (79) 297Chapter 17. KIT/PDGFR/Multkinase Inhibitors 29917.1 Avapritinib* (80) 30117.2 Ripretinib* (81) 304Chapter 18. FLT3 Inhibitors 30618.1 Midostaurin* (82) 30818.2 Gilteritinib* (83) 313Chapter 19. mTOR Inhibitors 31519.1 Sirolimus* and Analogs (84) 317Chapter 20. Other Kinase Inhibitors 32220.1 Netarsudil* (85) 32420.2 Belumosudil* (86) 32620.3 Fostamatinib* (87) 32820.4 Pexidartinib* (88) 331Chapter 21. KRAS Inhibitors 33521.1 Sotorasib* (89) 33721.2 Adagrasib* (90) 34621.3 Jdq443 # (91) 350Chapter 22. An Overview of the Discovery Process for Medically Useful Inhibitors of Oncogenic Protein Kinases 35322.1 High-quality Leads 35322.2 Integrating Substructures from Different High Quality Leads or Established Inhibitors 35522.3 Variation of Hinge-binding Nucleus 35722.4 Macrocyclization 35922.5 Fragment-based Approach 36022.6 Covalent Inhibitors 36122.7 Strategic Structural Modification of Prior Drugs 36222.8 Exploiting a Specific Kinase Pocket to Optimize Selectivity 36422.9 Solvent-exposed Appendages to Enhance Solubility and PK Properties 367Chapter 23. Targeted Molecular Anticancer Therapies - Successes and Challenges 36823.1 The Beginning 36823.2 Further Developments 36823.3 Biomarker-driven Drug Development 36923.4 Mitigation of Drug Resistance 37023.5 Miscellaneous Approaches 37123.6 Discovery Chemistry 373Appendix 1. First FDA Approvals by Year 374Appendix 2. Kinase/KRAS Inhibitors in Development 375Appendix 3. Visualization of Differentially Expressed Kinases in Cancer 378Appendix 4. M & A Transactions Driven by Oncology-focused Kinase and KRAS Inhibitors 379Appendix 5. Alphabetic List of Oncogenic Protein Inhibitors 380

O autorze

E.J. Corey has been a Professor at Harvard University since 1959. He was educated at The Massachusetts Institute of Technology (1945-1950) and served as a faculty member at the University of Illinois from 1951 to 1959. He is the 1990 Nobel Laureate in Chemistry. He has received many international awards including the U.S. National Medal of Science, the Japan Prize, the Wolf Prize and the Priestley Medal of the American Chemical Society, and many honorary degrees including DSc degrees from Oxford and Cambridge. He is a member of the U.S. National Academy of Sciences and the U.S. National Academy of Medicine. Professor Corey is the author of more than 1,000 publications and is one of the most cited authors in science. Among his previous books are The Logic of Chemical Synthesis (1989), Molecules and Medicine (2007) and Enantioselective Chemical Synthesis (2010).??Yong-Jin Wu is a medicinal chemist in the pharmaceutical industry with over 25 years of industry experience. He received his B.Sc. in chemistry from Hunan Normal University (Changsha, China) in 1983 and his Ph.D. in organic chemistry from Memorial University of Newfoundland in 1991 under Professor Jean Burnell. Subsequently, he undertook postdoctoral training in natural product synthesis with Professor Derrick Clive at the University of Alberta (1991-1992) and Professor E. J. Corey at Harvard University (1992-1995). He started his career as a medicinal chemist at Pfizer Central Research in Groton, CT in 1995 and joined Bristol Myers Squibb (BMS) in Wallingford, CT in 1999. He has been working at BMS ever since and currently is at the Cambridge, MA facility where his investigations focus on the discovery of novel kinase inhibitors for immunology, rheumatology and oncology indications.