Overcoming Obstacles in Drug Discovery and Development

Preface Kan He, Paul Frederick Hollenberg and Larry C. Wienkers 1. Learning to think critically Brian Barnes 2. Leveraging ADME/PK information to enable knowledge-driven decisions in drug discovery and development Larry C. Wienkers 3. Systems biology and data science in research and translational medicine Karim Azer, Jeff S. Barrett, Mirjam Trame and Cynthia J. Musante 4. Drug Discovery and Development of ASO Brooke Rock 5. Drug development of covalent Inhibitors Upendra P. Dahal and Jan L. Wahlstrom 6. Denosumab: dosing and drug interaction challenges on the path to approval Graham Jang 7. Discovery and development of ADCs: obstacles and opportunities Hsuan Ping Chang, Yuen Kiu Cheung and Dhaval K. Shah 8. How to reduce risk of drug induced liver toxicity from the beginning Jinping Gan, Kan He and W. Griffith Humphreys 9. Optimization for small volume of distribution leading to the discovery of apixaban Kan He 10. Design, conduct, and interpretation of human mass balance studies and strategies for assessing metabolites-in-safety testing (MIST) in drug development Simon G. Wong and Shuguang Ma 11. Conquering low oral bioavailability issues in drug discovery and development Timothy J. Carlson 12. Case study of OATP1B DDI assessment and challenges in drug discovery and development-real-life examples Hong Shen, Jinping Gan and Giridhar S. Tirucherai 13. Investigating the link between drug metabolism and toxicity W. Griffith Humphreys 14. Overcoming nephrotoxicity in rats: the successful development and registration of the HIV-AIDS drug efavirenz (Sustiva®) D.D. Christ 15. Disproportionate drug metabolites: challenges and solutions Chandra Prakash 16. Disposition and metabolism of ozanimod-Surmounting the unanticipated challenge late in the development Deepak Dalvie and Sekhar Surapaneni 17. Application of reaction phenotyping to address pharmacokinetic variability in patient populations Robert S. Foti, Joseph M. Roesner and Joshua T. Pearson 18. Kyprolis (carfilzomib) (approved): a covalent drug with high extrahepatic clearance via peptidase cleavage and epoxide hydrolysis Zhengping Wang, Jinfu Yang an Christopher Kirk 19. Engaging diversity in research: Does your drug work in overlooked populations? Karen E. Brown and Erica L. Woodahl 20. PBPK modeling for Early clinical study decision making Arian Emami Riedmaier 21. Integrated pharmacokinetic/pharmacodynamic/efficacy analysis in oncology: importance of pharmacodynamic/efficacy relationships Harvey Wong 22. Predicting unpredictable human pharmacokinetics: Case studies from the trenches of drug discovery Zheng Yang 23. Esmolol (soft drug design) Paul W. Erhardt