Overcoming Obstacles in Drug Discovery and Development

Surmounting the Insurmountable—Case Studies for Critical Thinking

Kan He, Paul F. Hollenberg, Larry C. Wienkers

• Publisher: Academic Press
• Year: 2023
• Print ISBN:
  9780128171349
• eBook ISBN:
  9780128173398
• Topic: Medicine
• Subtopic: Pharmaceutical, Biotechnology & Healthcare Industry

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

• Title of Book
• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter 1 Learning to think critically
• Chapter 2 Leveraging ADME/PK information to enable knowledge-driven decisions in drug discovery and development
• Chapter 3 Systems biology and data science in research and translational medicine
• Chapter 4 ADME considerations for siRNA-based therapeutics
• Chapter 5 Drug development of covalent inhibitors
• Chapter 6 Denosumab: dosing and drug interaction challenges on the path to approval
• Chapter 7 Discovery and development of ADCs: obstacles and opportunities
• Chapter 8 How to reduce risk of drug induced liver toxicity from the beginning
• Chapter 9 Optimization for small volume of distribution leading to the discovery of apixaban
• Chapter 10 Design, conduct, and interpretation of human mass balance studies and strategies for assessing metabolites-in-safety testing (MIST) in drug development
• Chapter 11 Conquering low oral bioavailability issues in drug discovery and development
• Chapter 12 Case study of OATP1B DDI assessment and challenges in drug discovery and development—real-life examples
• Chapter 13 Investigating the link between drug metabolism and toxicity
• Chapter 14 Overcoming nephrotoxicity in rats: the successful development and registration of the HIV-AIDS drug efavirenz (Sustiva®)
• Chapter 15 Disproportionate drug metabolites: challenges and solutions
• Chapter 16 Disposition and metabolism of ozanimod–Surmounting the unanticipated challenge late in development
• Chapter 17 Application of reaction phenotyping to address pharmacokinetic variability in patient populations
• Chapter 18 Kyprolis (carfilzomib) (approved): a covalent drug with high extrahepatic clearance via peptidase cleavage and epoxide hydrolysis
• Chapter 19 Engaging diversity in research: does your drug work in overlooked populations?
• Chapter 20 PBPK modeling for early clinical study decision making
• Chapter 21 Integrated pharmacokinetic/pharmacodynamic/efficacy analysis in oncology: importance of pharmacodynamic/efficacy relationships
• Chapter 22 Predicting unpredictable human pharmacokinetics: case studies from the trenches of drug discovery
• Chapter 23 Esmolol (soft drug design)
• Index