The Design of Covalent-Based Inhibitors
- 1st Edition, Volume 56 - July 9, 2021
- Imprint: Academic Press
- Editors: Richard A Ward, Neil Grimster
- Language: English
- Hardback ISBN:9 7 8 - 0 - 1 2 - 8 2 1 6 8 9 - 7
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 2 3 2 4 6 - 0
Annual Report on Medicinal Chemistry series, highlights new advances in the field with this new volume presenting interesting chapters. Each chapter is written by an intern… Read more
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Request a sales quoteAnnual Report on Medicinal Chemistry series, highlights new advances in the field with this new volume presenting interesting chapters. Each chapter is written by an international board of authors.
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Undergraduates, graduates, academics, and researchers in the field of medicinal chemistry
- Cover image
- Title page
- Table of Contents
- Copyright
- Contributors
- Preface
- Chapter One: Kinetic mechanisms of covalent inhibition
- Abstract
- 1: Introduction
- 2: Mechanisms
- 3: Data analysis techniques
- 4: Experimental techniques
- 5: Summary
- Acknowledgment
- Chapter Two: Covalent drugs in development for immune-mediated diseases
- Abstract
- 1: Introduction
- 2: Developing covalent kinase inhibitors for immune-mediated diseases
- 3: Evobrutinib—Multiple sclerosis
- 4: BMS-986195 (Branebrutinib): Preclinical safety and efficacy determination to Ph I clinical trials
- 5: LOU064 (Remibrutinib): Preclinical safety and efficacy determination to Ph I clinical trials
- 6: PRN1008 in clinical trials
- 7: Conclusion
- Chapter Three: Chemistry perspectives of reversible covalent drugs
- Abstract
- 1: Introduction
- 2: Prominent examples of RCDs
- 3: Thermodynamic considerations of RCD design
- 4: Kinetic considerations of RCD design
- 5: Challenges and future perspectives
- 6: Conclusion
- Acknowledgments
- Chapter Four: Design of next-generation covalent inhibitors: Targeting residues beyond cysteine
- Abstract
- 1: Introduction
- 2: Lysine (and N-terminal amine)
- 3: Tyrosine
- 4: Histidine
- 5: Serine, threonine
- 6: Others (glutamate, aspartate, methionine)
- 7: Conclusions and future opportunities
- Competing interests
- Chapter Five: Boron and covalent inhibition
- Abstract
- 1: General design principles—Covalent and non-covalent approaches
- 2: Designing for efficacy
- 3: Designing for pharmacokinetic and chemical stability
- 4: Designing for safety
- 5: Opportunities and inspiration from nature
- 6: Concluding comments
- Chapter Six: Measuring and predicting warhead and residue reactivity
- Abstract
- 1: Introduction
- 2: Physical parameters of covalent inhibition
- 3: Predicting warhead reactivity
- 4: Limitations of descriptor-based analysis
- 5: Conclusions and future directions
- Chapter Seven: Computational support of structure-based targeted covalent inhibitor design
- Abstract
- 1: Introduction
- 2: TCI advantages
- 3: Computational support of structure-based TCI design
- 4: Conclusions
- Chapter Eight: Covalent fragment screening
- Abstract
- 1: Covalent fragment screening
- 2: Covalent fragment libraries
- 3: Commercial covalent fragment libraries
- 4: Notable successful applications of covalent fragment screening
- 5: Chemoproteomic fragment screens
- 6: Conclusions and outlook
- Chapter Nine: The future of covalent inhibition
- Abstract
- 1: New electrophilic warheads
- 2: Covalent fragment approaches
- 3: Covalent PROTAC methods
- 4: Covalent proteomics and phenotypic approaches
- 5: Novel target types
- 6: Conclusion
- Edition: 1
- Volume: 56
- Published: July 9, 2021
- No. of pages (Hardback): 298
- No. of pages (eBook): 298
- Imprint: Academic Press
- Language: English
- Hardback ISBN: 9780128216897
- eBook ISBN: 9780128232460
RW
Richard A Ward
Richard A. Ward is at AstraZeneca, UK
Affiliations and expertise
AstraZeneca, UKNG
Neil Grimster
Neil Grimster is at AstraZeneca, USA
Affiliations and expertise
AstraZeneca, USARead The Design of Covalent-Based Inhibitors on ScienceDirect