Drug Discovery Stories, Volume Two showcases the discovery journeys of recent blockbuster drugs approved between 2023 and 2024, along with promising drug candidates. This book delves into structural biology, biological functions of targets, hit compound identification, hit-to-lead optimization, binding modes, key biological and pharmacokinetic data, and clinical results. It also covers other candidate compounds against the same targets and includes additional content based on the authors' choices. The series addresses the rapid evolution in drug discovery and development, appealing to those in chemical biology, synthetic chemistry, and pharmacology.
By highlighting interdisciplinary collaboration, the authors plan to release updated editions every few years to ensure the content reflects the latest achievements and breakthroughs in the field.
1. Title of Book - p. i 2. Cover image - p. i 3. Title page - p. ii 4. Table of Contents - p. iii 5. Copyright - p. iv 6. List of contributors - p. xix 7. About the editors - p. xxvii 8. Foreword - p. xxix 9. Preface - p. xxxi 10. Chapter 1. Piet De Somer (1917–85): a scientific career - p. 1 11. Chapter 2. Sculpting the future: harnessing artificial intelligence for revolutionary drug discovery - p. 15 12. Chapter 3. The role of early development as key success factor for drug discovery and development - p. 47 13. Chapter 4. Conception of antivirals: a historical perspective - p. 51 14. Chapter 5. Azvudine: a reverse transcriptase inhibitor for AIDS and COVID-19 treatment - p. 63 15. Chapter 6. Ensitrelvir: an oral noncovalent nonpeptidic SARS-CoV-2 main protease inhibitor with potent clinical effect - p. 79 16. Chapter 7. Leritrelvir (RAY1216): a novel α-ketoamide-based peptidomimetic inhibitor of SARS-CoV-2 main protease for COVID-19 treatment - p. 91 17. Chapter 8. Remdesivir: an early repurposed RNA-dependent RNA polymerase inhibitor for treating COVID-19 - p. 101 18. Chapter 9. Cabotegravir as an HIV-1 integrase strand transfer inhibitor: from workbench to clinical development - p. 115 19. Chapter 10. Uncovering the main hepatitis B virus receptor, sodium taurocholate cotransporting polypeptide, and its sequel to promising clinical trials with bulevirtide - p. 131 20. Chapter 11. The journey of highly potent dengue virus inhibitor, JNJ-A07 and JNJ-1802 from lab to clinic - p. 147 21. Chapter 12. Benzoxaborole drugs in therapy: successful cases of Tavaborole and Crisaborole - p. 165 22. Chapter 13. Enmetazobactam: an extended-spectrum beta-lactamase inhibitor in countering antimicrobial resistance - p. 181 23. Chapter 14. Taniborbactam (VNRX-5133): a broad-spectrum serine- and metallo-β-lactamase inhibitor for carbapenem-resistant bacterial infections - p. 193 24. Rezafungin: A β-(1,3)-D-glucan synthase inhibitor as antifungal drug derived from Echinocandin B0 - p. 207 25. Chapter 16. Beyond bedaquiline: the new generation of mycobacterial adenosine triphosphate synthase inhibitors TBAJ-587, TBAJ-876, and WX-081 for the treatment of drug-resistant tuberculosis - p. 225 26. Chapter 17. Fexinidazole: a chink in the armor of human African trypanosomiasis - p. 247 27. Chapter 18. Chiglitazar/Carfloglitazar, a drug for the treatment of type 2 diabetes mellitus and more - p. 259 28. Chapter 19. Semaglutide: a glucagon-like peptide-1 receptor agonist and its therapeutic potential in type 2 diabetes and beyond - p. 275 29. Chapter 20. Danuglipron: pioneering oral glucagon-like peptide-1 receptor agonists paving the way forrevolutionizing diabetes treatment - p. 293 30. Chapter 21. Donepezil: cholinesterase inhibitor for the treatment of Alzheimer's disease - p. 307 31. Chapter 22. Roflumilast: a selective phosphodiesterase-4 inhibitor for the treatment of Alzheimer’s disease - p. 323 32. Chapter 23. Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia - p. 331 33. Chapter 24. Gepirone: a selective partial agonist of the 5-HT1A receptor in the treatment of depression - p. 345 34. Chapter 25. Olverembatinib: a potent Bcr-Abl third-generation inhibitor for the treatment of chronic myeloid leukemia - p. 365 35. Chapter 26. STX-478, RLY-2608, and LOXO-783: third-generation PIK3CA mutant-selective allosteric inhibitors - p. 373 36. Chapter 27. Repotrectinib (TPX-0005): a macrocyclic ALK/ROS1/TRK inhibitor for the treatment of nonsmall cell lung cancer - p. 395 37. Chapter 28. FRUZAQLA (fruquintinib): a selective oral inhibitor of VEGFR -1, -2, and -3 for treating adults with metastatic colorectal cancer - p. 413 38. Chapter 29. RNK-05047: a chaperone-mediated protein degrader that selectively targets BRD4 while recruiting the HSP90 chaperone - p. 435 39. Chapter 30. Belzutifan: a first-in-class oral HIF-2α inhibitor approved for patients with von Hippel-Lindau disease-associated renal cell carcinoma - p. 449 40. Chapter 31. JPH-203: a LAT1 inhibitor as a promising solution for advanced refractory biliary tract cancer - p. 461 41. Chapter 32. Fluzoparib: the first Chinese original poly(ADP-ribose)polymerase inhibitor for the treatment of BRCA1/2 mutated ovarian cancer - p. 477 42. Chapter 33. Idecabtagene vicleucel: the first BCMA-targeted CAR-T cell therapy for multiple myeloma - p. 491 43. Chapter 34. NX-5948: a Bruton’s tyrosine kinase degrader in Ph. Ia/Ib for patients with advanced B-cell malignancies - p. 505 44. Chapter 35. Fingolimod (Gilenya): a sphingosine-1-phosphate receptor modulator for the treatment of multiple sclerosis - p. 519 45. Chapter 36. Momelotinib: a new frontier as a JAK1 and JAK2 inhibitor in hematological disorders - p. 533 46. Chapter 37. Imetelstat: a first-in-class telomerase inhibitor for treating myelodysplastic syndromes - p. 547 47. Chapter 38. Zanubrutinib in liquid cancers a new horizon - p. 553 48. Chapter 39. Piflufolastat F-18, Illuccix, Posluma, Pluvicto, and beyond: the development of radiopharmaceuticals for prostate cancer theranostics - p. 565 49. Chapter 40. Daprodustat (GSK-1278863): a small molecule hypoxia inducible factor-prolyl hydroxylase inhibitor for anemia - p. 583 50. Chapter 41. FABHALTA (iptacopan): an innovative advancement in the treatment of paroxysmal nocturnal hemoglobinuria - p. 603 51. Chapter 42. Resmetirom: a first-in-class thyroid hormone receptor β agonist approved by FDA for patients with nonalcoholic steatohepatitis - p. 619 52. Chapter 43. Fezolinetant: the first FDA-approved neurokinin-3 receptor antagonist for treating moderate-to-severe vasomotor symptoms associated with menopause - p. 633 53. Chapter 44. Nerandomilast (BI 1015550): an efficient PDE4 inhibitor for the potential treatment of idiopathic pulmonary fibrosis - p. 657 54. Chapter 45. Vamorolone: a dissociative steroid for the treatment of Duchenne muscular dystrophy - p. 671 55. Chapter 46. Sotagliflozin: a dual SGLT1/2 inhibitor, for full range of heart failure - p. 681 56. Drug development based on natural products of Euphorbia genus - p. 691 57. Index - p. 705
Drug Discovery Stories, Volume Two showcases the discovery journeys of recent blockbuster drugs approved between 2023 and 2024, along with promising drug candidates. This book delves into structural biology, biological functions of targets, hit compound identification, hit-to-lead optimization, binding modes, key biological and pharmacokinetic data, and clinical results. It also covers other candidate compounds against the same targets and includes additional content based on the authors' choices. The series addresses the rapid evolution in drug discovery and development, appealing to those in chemical biology, synthetic chemistry, and pharmacology.
By highlighting interdisciplinary collaboration, the authors plan to release updated editions every few years to ensure the content reflects the latest achievements and breakthroughs in the field.
1. Title of Book - p. i 2. Cover image - p. i 3. Title page - p. ii 4. Table of Contents - p. iii 5. Copyright - p. iv 6. List of contributors - p. xix 7. About the editors - p. xxvii 8. Foreword - p. xxix 9. Preface - p. xxxi 10. Chapter 1. Piet De Somer (1917–85): a scientific career - p. 1 11. Chapter 2. Sculpting the future: harnessing artificial intelligence for revolutionary drug discovery - p. 15 12. Chapter 3. The role of early development as key success factor for drug discovery and development - p. 47 13. Chapter 4. Conception of antivirals: a historical perspective - p. 51 14. Chapter 5. Azvudine: a reverse transcriptase inhibitor for AIDS and COVID-19 treatment - p. 63 15. Chapter 6. Ensitrelvir: an oral noncovalent nonpeptidic SARS-CoV-2 main protease inhibitor with potent clinical effect - p. 79 16. Chapter 7. Leritrelvir (RAY1216): a novel α-ketoamide-based peptidomimetic inhibitor of SARS-CoV-2 main protease for COVID-19 treatment - p. 91 17. Chapter 8. Remdesivir: an early repurposed RNA-dependent RNA polymerase inhibitor for treating COVID-19 - p. 101 18. Chapter 9. Cabotegravir as an HIV-1 integrase strand transfer inhibitor: from workbench to clinical development - p. 115 19. Chapter 10. Uncovering the main hepatitis B virus receptor, sodium taurocholate cotransporting polypeptide, and its sequel to promising clinical trials with bulevirtide - p. 131 20. Chapter 11. The journey of highly potent dengue virus inhibitor, JNJ-A07 and JNJ-1802 from lab to clinic - p. 147 21. Chapter 12. Benzoxaborole drugs in therapy: successful cases of Tavaborole and Crisaborole - p. 165 22. Chapter 13. Enmetazobactam: an extended-spectrum beta-lactamase inhibitor in countering antimicrobial resistance - p. 181 23. Chapter 14. Taniborbactam (VNRX-5133): a broad-spectrum serine- and metallo-β-lactamase inhibitor for carbapenem-resistant bacterial infections - p. 193 24. Rezafungin: A β-(1,3)-D-glucan synthase inhibitor as antifungal drug derived from Echinocandin B0 - p. 207 25. Chapter 16. Beyond bedaquiline: the new generation of mycobacterial adenosine triphosphate synthase inhibitors TBAJ-587, TBAJ-876, and WX-081 for the treatment of drug-resistant tuberculosis - p. 225 26. Chapter 17. Fexinidazole: a chink in the armor of human African trypanosomiasis - p. 247 27. Chapter 18. Chiglitazar/Carfloglitazar, a drug for the treatment of type 2 diabetes mellitus and more - p. 259 28. Chapter 19. Semaglutide: a glucagon-like peptide-1 receptor agonist and its therapeutic potential in type 2 diabetes and beyond - p. 275 29. Chapter 20. Danuglipron: pioneering oral glucagon-like peptide-1 receptor agonists paving the way forrevolutionizing diabetes treatment - p. 293 30. Chapter 21. Donepezil: cholinesterase inhibitor for the treatment of Alzheimer's disease - p. 307 31. Chapter 22. Roflumilast: a selective phosphodiesterase-4 inhibitor for the treatment of Alzheimer’s disease - p. 323 32. Chapter 23. Omaveloxolone: a nuclear factor erythroid 2-related factor 2 activator for Friedreich’s ataxia - p. 331 33. Chapter 24. Gepirone: a selective partial agonist of the 5-HT1A receptor in the treatment of depression - p. 345 34. Chapter 25. Olverembatinib: a potent Bcr-Abl third-generation inhibitor for the treatment of chronic myeloid leukemia - p. 365 35. Chapter 26. STX-478, RLY-2608, and LOXO-783: third-generation PIK3CA mutant-selective allosteric inhibitors - p. 373 36. Chapter 27. Repotrectinib (TPX-0005): a macrocyclic ALK/ROS1/TRK inhibitor for the treatment of nonsmall cell lung cancer - p. 395 37. Chapter 28. FRUZAQLA (fruquintinib): a selective oral inhibitor of VEGFR -1, -2, and -3 for treating adults with metastatic colorectal cancer - p. 413 38. Chapter 29. RNK-05047: a chaperone-mediated protein degrader that selectively targets BRD4 while recruiting the HSP90 chaperone - p. 435 39. Chapter 30. Belzutifan: a first-in-class oral HIF-2α inhibitor approved for patients with von Hippel-Lindau disease-associated renal cell carcinoma - p. 449 40. Chapter 31. JPH-203: a LAT1 inhibitor as a promising solution for advanced refractory biliary tract cancer - p. 461 41. Chapter 32. Fluzoparib: the first Chinese original poly(ADP-ribose)polymerase inhibitor for the treatment of BRCA1/2 mutated ovarian cancer - p. 477 42. Chapter 33. Idecabtagene vicleucel: the first BCMA-targeted CAR-T cell therapy for multiple myeloma - p. 491 43. Chapter 34. NX-5948: a Bruton’s tyrosine kinase degrader in Ph. Ia/Ib for patients with advanced B-cell malignancies - p. 505 44. Chapter 35. Fingolimod (Gilenya): a sphingosine-1-phosphate receptor modulator for the treatment of multiple sclerosis - p. 519 45. Chapter 36. Momelotinib: a new frontier as a JAK1 and JAK2 inhibitor in hematological disorders - p. 533 46. Chapter 37. Imetelstat: a first-in-class telomerase inhibitor for treating myelodysplastic syndromes - p. 547 47. Chapter 38. Zanubrutinib in liquid cancers a new horizon - p. 553 48. Chapter 39. Piflufolastat F-18, Illuccix, Posluma, Pluvicto, and beyond: the development of radiopharmaceuticals for prostate cancer theranostics - p. 565 49. Chapter 40. Daprodustat (GSK-1278863): a small molecule hypoxia inducible factor-prolyl hydroxylase inhibitor for anemia - p. 583 50. Chapter 41. FABHALTA (iptacopan): an innovative advancement in the treatment of paroxysmal nocturnal hemoglobinuria - p. 603 51. Chapter 42. Resmetirom: a first-in-class thyroid hormone receptor β agonist approved by FDA for patients with nonalcoholic steatohepatitis - p. 619 52. Chapter 43. Fezolinetant: the first FDA-approved neurokinin-3 receptor antagonist for treating moderate-to-severe vasomotor symptoms associated with menopause - p. 633 53. Chapter 44. Nerandomilast (BI 1015550): an efficient PDE4 inhibitor for the potential treatment of idiopathic pulmonary fibrosis - p. 657 54. Chapter 45. Vamorolone: a dissociative steroid for the treatment of Duchenne muscular dystrophy - p. 671 55. Chapter 46. Sotagliflozin: a dual SGLT1/2 inhibitor, for full range of heart failure - p. 681 56. Drug development based on natural products of Euphorbia genus - p. 691 57. Index - p. 705
