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

Molecules Engineered Against Oncogenic Proteins and Cancer
 
A comprehensive review of the latest molecular advances in cancer treatment
 
Featuring 91 total small molecule kinase/KRAS inhibitors, 80 of which are FDA-approved, Molecules Engineered Against Oncogenic Proteins and Cancer documents the recent scientific advances that have transformed one of medicine's most challenging areas--cancer treatment. Most of these inhibitors specifically block oncogene-induced carcinogenic proteins with results that have dramatically advanced the treatment of cancer. In addition, the structural formulas of more than 100 kinase/KRAS inhibitors in clinical trials are presented.
 
With a very well-known chemist as an author, Molecules Engineered Against Oncogenic Proteins and Cancer includes information on:
* Each molecule's structure, function of the kinase target and relevance to cancer, the drug discovery process, and molecular details of drug action
* Mutated protein kinases as oncoproteins and targets for inhibition, along with the details of discovery for each antitumor antikinase agent
* History of oncoprotein inhibitors and their role in advancing the treatment and understanding of cancer
* The discovery process as a whole, effective strategies for innovation, ongoing challenges, and a glimpse of the future of the field
 
Combining the most significant recent discoveries in a unique and useful way, Molecules Engineered Against Oncogenic Proteins and Cancer is an essential resource for researchers and students in bioscience, medicine, chemistry, and oncology as well as for those at industrial companies involved in therapeutic discovery.

List of contents

Preface vii
 
Chapter 1. Introduction 1
 
1.1 Types of Protein Kinases 1
 
1.2 Protein Kinase Domains 1
 
1.3 ATP-Binding Site 2
 
1.4 Types of Kinase Inhibitors 3
 
1.5 Brief History of Smallmolecule Kinase Inhibitors 5
 
1.6 Peak 12-Month Sales for Leading Kinase Inhibitors 7
 
1.7 Approved Kinase Inhibitors 7
 
Chapter 2. BCR-ABL Inhibitors 18
 
2.1 Imatinib* (1) 19
 
2.2 Nilotinib* (2) 24
 
2.3 Dasatinib* (3) 27
 
2.4 Bosutinib* (4) 30
 
2.5 Ponatinib* (5) 33
 
2.6 Olvermbatinib** (6) 37
 
2.7 Asciminib* (7) 38
 
Chapter 3. BTK Inhibitors 43
 
3.1 Ibrutinib* (8) 45
 
3.2 Acalabrutinib* (9) 51
 
3.3 Zanubrutinib* (10) 54
 
3.4 Tirabrutinib** (11) 57
 
3.5 Orelabrutinib** (12) 58
 
Chapter 4. EGFR/HER Family Inhibitors 59
 
4.1 Gefitinib* (13) 61
 
4.2 Erlotinib * (14) 67
 
4.3 Icotinib** (15) 72
 
4.4 Afatinib* (16) 74
 
4.5 Dacomitinib* (17) 77
 
4.6 Osimertinib* (18) 80
 
4.7 Mobocertinib* (19) 86
 
4.8 Lapatinib* (20) 90
 
4.9 Tucatinib* (21) 93
 
4.10 Neratinib* (22) 95
 
Chapter 5. VEGFR/Multikinase Inhibitors 97
 
5.1 Sorafenib* (23) 99
 
5.2 Regorafenib* (24) 104
 
5.3 Sunitinib* (25) 106
 
5.4 Pazopanib* (26) 112
 
5.5 Axitinib* (27) 114
 
5.6 Nintedanib* (28) 117
 
5.7 Apatinib** (29) 121
 
5.8 Lenvatinib* (30) 122
 
5.9 Tovozanib* (31) 125
 
Chapter 6. CDK4/6 Inhibitors 127
 
6.1 Palbociclib* (32) 129
 
6.2 Ribociclib*(33) 136
 
6.3 Abemaciclib* (34) 139
 
6.4 Trilaciclib* (35) 142
 
Chapter 7. JAK Inhibitors 144
 
7.1 Tofacitinib* (36) 147
 
7.2 Baricitinib* (37) 151
 
7.3 Peficitinib** (38) 153
 
7.4 Upadacitinib* (39) 158
 
7.5 Delgocitinib** (40) 161
 
7.6 Filgotinib** (41) 163
 
7.7 Abrocitinib* (42) 166
 
7.8 Ruxolitinib* (43) 170
 
7.9 Fedratinib* (44) 173
 
7.10 Pacritinib* (45) 175
 
7.11 Ritlecitinib # (46) 177
 
7.12 Brepocitinib # (47) 181
 
7.13 Ropsacitinib # (48) 184
 
Chapter 8. Allosteric TYK2 Inhibitors 187
 
8.1 Deucravacitinib* (49) 189
 
Chapter 9. ALK/multikinase Inhibitors 195
 
9.1 Crizotinib* (50) 197
 
9.2 Ceritinib* (51) 202
 
9.3 Alectinib* (52) 205
 
9.4 Brigatinib* (53) 207
 
9.5 Lorlatinib* (54) 210
 
Chapter 10. BRAF/Multikinase Inhibitors 214
 
10.1 Vemurafenib* (55) 216
 
10.2 Dabrafenib* (56) 222
 
10.3 Encorafenib* (57) 225
 
Chapter 11. MEK Inhibitors 227
 
11.1 Trametinib* (58) 228
 
11.2 Cobimetinib* (59) 232
 
11.3 Binimetinib* (60) 235
 
11.4 Selumetinib* (61) 237
 
Chapter 12. RET/Multikinase Inhibitors 240
 
12.1 Vandetanib* (62) 242
 
12.2 Cabozantinib* (63) 245
 
12.3 Selpercatinib* (64) 247
 
12.4 Pralsetinib* (65) 251
 
Chapter 13. FGFR Inhibitors 253
 
13.1 Erdafitinib* (66) 255
 
13.2 Pemigatinib* (67) 260
 
13.3 Infigratinib* (68) 263
 
13.4 Futibatinib* (69) 265
 
Chapter 14. PI3K Inhibitors 267
 
14.1 Alpelisib* (70) 269
 
14.2 Idelalisib* (71) 273
 
14.3 Duvelisib* (72) 277
 
14.4 Umbralisib* (73) 279
 
14.5 Copanlisib* (74) 281
 
Chapter 15. TRK/Multikinase Inhibitors 284
 
15.1 Larotrectinib* (75) 285
 

About the author

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.

Product details

• Authors: E J Corey, E. J. Corey, E. J. (Harvard University Corey, Corey E. J., Yong-Jin Wu
• Publisher: Wiley, John and Sons Ltd
• Languages: English
• Product format: Hardback
• Released: 09.08.2023
• EAN: 9781394207084
• ISBN: 978-1-394-20708-4
• No. of pages: 400
• Subjects: Natural sciences, medicine, IT, technology > Chemistry > Organic chemistry; Chemie, Organische Chemie, Medizin, Pharmakologie, ORGANIC CHEMISTRY, chemistry, Pharmacology & Pharmaceutical Medicine, Pharmakologie u. Pharmazeutische Medizin, Medical Science, Pharmaceutical & Medicinal Chemistry, Pharmazeutische u. Medizinische Chemie