Description
Overcoming Obstacles in Drug Discovery and Development uses real-world case studies to illustrate how critical thinking and problem solving skills are applied in the discovery and development of drugs. It also shows how developing critical thinking to overcome issues plays an essential role in the process. Modern drug discovery and development is a highly complex undertaking that requires scientific and professional expertise to be successful. After the identification of a molecular entity for treating a medical condition, challenges inevitably arise during the subsequent development to understand and characterize the biological profile; feedback from scientists is used to fine-tune the molecular entity to obtain an effective and safe product. In this process, the discovery team may identify unexpected safety issues and new medical disorders for treatment by the molecular entity. Invariably inherent in this complex undertaking are miscues, mistakes, and unexpected problems that can derail development and throw timetables into disarray, potentially leading to failure in the development of a medically useful drug. Addressing critical unexpected problems during development often requires scientists to utilize critical thinking and imaginative problem-solving skills. Overcoming Obstacles in Drug Discovery and Development will be essential to young scientists to help learn the skills to successfully face challenges, learn from mistakes, and further develop critical thinking skills. It will also be beneficial to experienced researchers who can learn from the case studies of successful and unsuccessful drug development.- Provides real-world case studies in drug discovery and the development of drugs- Illustrates the use of critical thinking and problem solving in approaching preclinical and clinical problems in drug discovery and development- Illustrates and analyses examples of successes and failures in drug discovery and development that have not previously been reported
Table of Contents
PrefaceKan He, Paul Frederick Hollenberg and Larry C. Wienkers1. Learning to think criticallyBrian Barnes2. Leveraging ADME/PK information to enable knowledge-driven decisions in drug discovery and developmentLarry C. Wienkers3. Systems biology and data science in research and translational medicineKarim Azer, Jeff S. Barrett, Mirjam Trame and Cynthia J. Musante4. Drug Discovery and Development of ASOBrooke Rock5. Drug development of covalent InhibitorsUpendra P. Dahal and Jan L. Wahlstrom6. Denosumab: dosing and drug interaction challenges on the path to approvalGraham Jang7. Discovery and development of ADCs: obstacles and opportunitiesHsuan Ping Chang, Yuen Kiu Cheung and Dhaval K. Shah8. How to reduce risk of drug induced liver toxicity from the beginningJinping Gan, Kan He and W. Griffith Humphreys9. Optimization for small volume of distribution leading to the discovery of apixabanKan He10. Design, conduct, and interpretation of human mass balance studies and strategies for assessing metabolites-in-safety testing (MIST) in drug developmentSimon G. Wong and Shuguang Ma11. Conquering low oral bioavailability issues in drug discovery and developmentTimothy J. Carlson12. Case study of OATP1B DDI assessment and challenges in drug discovery and development—real-life examplesHong Shen, Jinping Gan and Giridhar S. Tirucherai13. Investigating the link between drug metabolism and toxicityW. Griffith Humphreys14. Overcoming nephrotoxicity in rats: the successful development and registration of the HIV-AIDS drug efavirenz (Sustiva®)D.D. Christ15. Disproportionate drug metabolites: challenges and solutionsChandra Prakash16. Disposition and metabolism of ozanimod—Surmounting the unanticipated challenge late in the developmentDeepak Dalvie and Sekhar Surapaneni17. Application of reaction phenotyping to address pharmacokinetic variability in patient populationsRobert S. Foti, Joseph M. Roesner and Joshua T. Pearson18. Kyprolis (carfilzomib) (approved): a covalent drug with high extrahepatic clearance via peptidase cleavage and epoxide hydrolysisZhengping Wang, Jinfu Yang an Christopher Kirk19. Engaging diversity in research: Does your drug work in overlooked populations?Karen E. Brown and Erica L. Woodahl20. PBPK modeling for Early clinical study decision makingArian Emami Riedmaier21. Integrated pharmacokinetic/pharmacodynamic/efficacy analysis in oncology: importance of pharmacodynamic/efficacy relationshipsHarvey Wong22. Predicting unpredictable human pharmacokinetics: Case studies from the trenches of drug discoveryZheng Yang23. Esmolol (soft drug design)Paul W. Erhardt
