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

· 제목 : Molecules Engineered Against Oncogenic Proteins and Cancer: Discovery, Design, and Development (Hardcover) 
· 분류 : 외국도서 > 의학 > 약리학
· ISBN : 9781394207084
· 쪽수 : 400쪽
· 출판일 : 2023-09-06

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

15.2 Entrectinib* (76) 288

15.3 Repotrectinib # (77) 291

Chapter 16. MET Inhibitors 294

16.1 Capmatinib* (78) 295

16.2 Tepotinib* (79) 297

Chapter 17. KIT/PDGFR/Multkinase Inhibitors 299

17.1 Avapritinib* (80) 301

17.2 Ripretinib* (81) 304

Chapter 18. FLT3 Inhibitors 306

18.1 Midostaurin* (82) 308

18.2 Gilteritinib* (83) 313

Chapter 19. mTOR Inhibitors 315

19.1 Sirolimus* and Analogs (84) 317

Chapter 20. Other Kinase Inhibitors 322

20.1 Netarsudil* (85) 324

20.2 Belumosudil* (86) 326

20.3 Fostamatinib* (87) 328

20.4 Pexidartinib* (88) 331

Chapter 21. KRAS Inhibitors 335

21.1 Sotorasib* (89) 337

21.2 Adagrasib* (90) 346

21.3 Jdq443 # (91) 350

Chapter 22. An Overview of the Discovery Process for Medically Useful Inhibitors of Oncogenic Protein Kinases 353

22.1 High-quality Leads 353

22.2 Integrating Substructures from Different High Quality Leads or Established Inhibitors 355

22.3 Variation of Hinge-binding Nucleus 357

22.4 Macrocyclization 359

22.5 Fragment-based Approach 360

22.6 Covalent Inhibitors 361

22.7 Strategic Structural Modification of Prior Drugs 362

22.8 Exploiting a Specific Kinase Pocket to Optimize Selectivity 364

22.9 Solvent-exposed Appendages to Enhance Solubility and PK Properties 367

Chapter 23. Targeted Molecular Anticancer Therapies – Successes and Challenges 368

23.1 The Beginning 368

23.2 Further Developments 368

23.3 Biomarker-driven Drug Development 369

23.4 Mitigation of Drug Resistance 370

23.5 Miscellaneous Approaches 371

23.6 Discovery Chemistry 373

Appendix 1. First FDA Approvals by Year 374

Appendix 2. Kinase/KRAS Inhibitors in Development 375

Appendix 3. Visualization of Differentially Expressed Kinases in Cancer 378

Appendix 4. M & A Transactions Driven by Oncology-focused Kinase and KRAS Inhibitors 379

Appendix 5. Alphabetic List of Oncogenic Protein Inhibitors 380