
Drug Discovery Stories
From Bench to Bedside
- 1st Edition - October 18, 2024
- Editors: Bin Yu, Peng Zhan
- Language: English
- Paperback ISBN:9 7 8 - 0 - 4 4 3 - 2 3 9 3 2 - 8
- eBook ISBN:9 7 8 - 0 - 4 4 3 - 2 3 9 3 3 - 5
Drug Discovery Stories: From Bench to Bedside presents a collection of cases on the development of highly successful pharmaceuticals. It delves into the realm of drug discovery… Read more

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Request a sales quoteDrug Discovery Stories: From Bench to Bedside presents a collection of cases on the development of highly successful pharmaceuticals. It delves into the realm of drug discovery, exploring the structural biology and biological functions of the sought-after targets. The book covers the identification of promising compounds, their transformation from hits to leads through meticulous optimization, and the elucidation of how key compounds interact with the target (in essence, providing invaluable insights for drug design). Additionally, it covers essential information such as the pivotal biological and PK data of lead compounds, any noteworthy clinical results, and a comprehensive overview of other candidate compounds.
The field of drug discovery and development has experienced rapid evolution, with numerous new drugs receiving approval each year. While several books have been published on this subject, there is a pressing need for a new book series that accurately reflects the current advancements in drug discovery. This book aims to not only cater to the drug discovery community but also engage other communities involved in chemical biology, synthetic chemistry, and pharmacology.
- Analyzes the drug discovery stories of different blockbuster drugs
- Includes the newly approved drugs
- Covers key aspects related to the drug development of the drugs
Graduate students and researchers working with Drug Discovery, Medicinal Chemistry, Chemical Biology and Synthetic Chemistry
- Title of Book
- Cover image
- Title page
- Table of Contents
- Copyright
- Dedication
- List of contributors
- About the editors
- Foreword 1
- Foreword 2
- 1 The genesis of drug discovery stories
- 2 Analyzing blockbuster drugs: a kaleidoscope of success
- 3 Newly approved drugs: pioneering the future of medicine
- 4 Key aspects of drug development: navigating the odyssey
- 5 Diversity in voices: a global mosaic of contributors
- 6 Embarking on a collective exploration
- Section 1: Drug discovery techniques and strategies
- Chapter 1. Artificial intelligence in early stages of structure-based drug discovery
- Abstract
- 1.1 Introduction
- 1.2 Target structure determination
- 1.3 Binding site elucidation
- 1.4 Chemical libraries
- 1.5 Structure-based virtual screening
- 1.6 Conclusions
- Acknowledgments
- References
- Chapter 2. Target-based vs phenotypic drug discovery: opportunities and challenges with evidence-based application
- Abstract
- Graphical abstract
- 2.1 Introduction
- 2.2 Phenotypic drug discovery
- 2.3 Opportunities and challenges in phenotypic drug discovery
- 2.4 Use of artificial intelligence to improve phenotypic drug discovery
- 2.5 Modern phenotypic drug discovery advancements
- 2.6 Target-based drug discovery
- 2.7 Target identification and validation
- 2.8 Challenges of target-based drug discovery
- 2.9 Conclusion and future perspectives
- References
- Chapter 3. Hit discovery from DNA-encoded chemical library
- Abstract
- 3.1 Principles of DNA-encoded chemical library
- 3.2 Introduction to encoding methods, DNA-compatible reactions, selection methods, and sequencing analysis
- 3.3 Case studies and summary
- 3.4 Summary and outlook of DNA-encoded chemical library in drug discovery
- References
- Chapter 4. Discovery of lead compounds from pseudo-natural macrocycles enabled by modular biomimetic strategy
- Abstract
- 4.1 Introduction
- 4.2 Method and proof of concept
- 4.3 Future perspectives and conclusion
- References
- Chapter 5. Macrocyclization strategy in kinase drug discovery
- Abstract
- 5.1 Introduction
- 5.2 Advantages of macrocyclization
- 5.3 Computational design strategy
- 5.4 Conclusion and perspectives
- References
- Chapter 6. Cobalt-catalyzed C–H functionalization for the synthesis of chiral heterocyclic molecules
- Abstract
- 6.1 Introduction
- 6.2 Conclusions
- Acknowledgments
- References
- Chapter 7. Advancing proteolysis targeting chimeras toward clinical drug developments
- Abstract
- 7.1 Introduction
- 7.2 Proteolysis targeting chimeras in clinical developments
- 7.3 Conclusions and outlooks
- Acknowledgments
- References
- Chapter 8. A future battle, small-molecule drugs for cancer stem cell targeted therapy
- Abstract
- 8.1 Introduction
- 8.2 Key signaling pathways in cancer stem cells
- 8.3 Key cancer stem cell markers and relating anticancer drugs
- 8.4 Existing problems and future perspective
- 8.5 New thoughts for targeting cancer stem cells
- 8.6 Conclusion
- Acknowledgments
- Declaration of interests
- Author contributions
- References
- Chapter 9. Stem cell therapies for combating emerging and reemerging viral infections
- Abstract
- 9.1 Introduction
- 9.2 Emerging and reemerging viral infections all over the world
- 9.3 Therapeutic achievements of stem cell therapy
- 9.4 Role of mesenchymal stem cells (MSCs) to prevent emerging and reemerging zoonotic viral infections
- 9.5 Stem cell therapy for the treatment and prevention of viral diseases
- 9.6 Stem cell therapy: a possible treatment for influenza and coronavirus-induced acute lung damage
- 9.7 T-cell therapy helps overcome stem cell transplant viral infections
- 9.8 Molecular mechanisms responsible for mesenchymal stem cell–based (MSCs) treatment of viral diseases
- 9.9 Clinical studies for Coronavirus disease 2019 stem cell therapy
- 9.10 Challenges and opportunities for MSC-based therapies in viral infections
- 9.11 Conclusion and future perspectives
- References
- Chapter 10. Targeting autophagy with pharmacological small molecules to treat human diseases
- Abstract
- 10.1 Introduction
- 10.2 Autophagy and human diseases
- 10.3 Discovery of pharmacological small molecules targeting autophagy
- 10.4 Discovery of pharmacological small molecules based on autophagic degradation strategies
- 10.5 Conclusions and perspectives
- Acknowledgments
- References
- Chapter 11. Interferons in human papillomavirus infection: antiviral effectors or immunopathogenic role?
- Abstract
- 11.1 Introduction
- 11.2 Human papillomavirus
- 11.3 Current and future directions in the treatment of human papillomavirus-related diseases
- 11.4 The interferon response
- 11.5 In vitro studies of the innate antiviral signaling pathways to human papillomavirus
- 11.6 In vivo studies of the innate antiviral response to human papillomavirus
- 11.7 Interferon as an antiviral drug for the treatment of human papillomavirus infection
- 11.8 Conclusion
- References
- Chapter 12. Selenium and small molecules: a symbiotic partnership
- Abstract
- 12.1 Introduction
- 12.2 One case study: ebselen
- 12.3 Conclusion
- Acknowledgments
- References
- Chapter 13. Novel combinations of CD33-targeted immunotherapies
- Abstract
- 13.1 CD33-targeted immunotherapies
- 13.2 Bridge to transplantation
- 13.3 Combination with small molecule
- 13.4 Novel combinations of CD33-targeted therapies
- 13.5 Conclusions
- Acknowledgments
- References
- Chapter 14. Novel payloads of antibody-drug conjugates
- Abstract
- 14.1 Background
- 14.2 proteolysis-targeting chimeras-based antibody–drug conjugate payloads
- 14.3 Dual-payload antibody–drug conjugates
- 14.4 Immune antibody–drug conjugate payloads
- 14.5 Other potential antibody-drug conjugate payloads
- 14.6 Conclusions and perspectives
- References
- Chapter 15. Antibody−drug conjugates: a new generation of cancer vaccines
- Abstract
- 15.1 Introduction
- 15.2 Development and generation of antibody drug conjugates
- 15.3 Structure and mechanism of antibody−drug conjugate
- 15.4 Discovery and drug design of antibody−drug conjugate
- 15.5 Challenges and limitations in clinical use
- 15.6 Clinical applications and efficacy
- 15.7 Next-generation antibody−drug conjugates
- 15.8 Concluding remarks and future directions
- References
- Chapter 16. mRNA vaccines: the next frontier in disease prevention
- Abstract
- 16.1 Introduction
- 16.2 The mRNA revolution
- 16.3 Conclusion and future directions
- References
- Chapter 17. Unravelling the drying techniques of protein biopharmaceuticals
- Abstract
- 17.1 Introduction
- 17.2 Biopharmaceutical products
- 17.3 Proteins—structure and configuration
- 17.4 Instability of protein-based biopharmaceutical products
- 17.5 Drying techniques for protein-based biopharmaceutical products
- 17.6 Stabilizers for protein-based biopharmaceutical products
- 17.7 Conclusion
- Acknowledgments
- References
- Section 2: Drug discovery case studies
- Chapter 18. Lenacapavir: a first-in-class HIV-1 capsid inhibitor for the treatment of multidrug-resistant HIV infections
- Abstract
- 18.1 Introduction
- 18.2 The discovery of HIV CA modulator LEN
- 18.3 Mechanism of action of HIV CA modulator LEN
- 18.4 Clinical trials of HIV CA modulator LEN
- 18.5 LEN’s breakthrough in drug discovery
- 18.6 Conclusion and perspective
- References
- Chapter 19. Nirmatrelvir, SIM0417, and RAY1216: potent and selective SARS-CoV-2 main protease inhibitors for the potential treatment of COVID-19
- Abstract
- 19.1 Introduction
- 19.2 Nirmatrelvir, SIM0417, and RAY1216 as SARS-CoV-2 Mpro inhibitors
- 19.3 Conclusion
- Acknowledgments
- References
- Chapter 20. Bavdegalutamide (ARV-110): a potent PROTAC androgen receptor degrader for the treatment of metastatic-castration resistant prostate cancer
- Abstract
- Abbreviations
- 20.1 Introduction
- 20.2 Androgen receptor and prostate cancer
- 20.3 Proteolysis targeting chimeras
- 20.4 Advances in PROTAC androgen receptor degraders
- 20.5 Discovery and development of ARV-110
- 20.6 Conclusion
- Acknowledgments
- References
- Further reading
- Chapter 21. Darolutamide: an androgen receptor antagonist for the treatment of prostate cancer
- Abstract
- Abbreviations
- 21.1 Introduction
- 21.2 Current available therapies for prostate cancer
- 21.3 Androgen receptor antagonists
- 21.4 Introduction to darolutamide
- 21.5 Clinical efficacy of darolutamide
- 21.6 Safety profile of darolutamde
- 21.7 Conclusion
- 21.8 Future perspective
- Acknowledgments
- Funding
- Conflict of interest
- References
- Chapter 22. Palbociclib, ribociclib, and abemaciclib: potent and selective CDK4/6 inhibitors for the treatment of breast cancer
- Abstract
- 22.1 Introduction
- 22.2 Targeting CDK4/6 for breast cancer treatment
- 22.3 CDK4/6 inhibitors for breast cancer
- 22.4 Drug combination
- 22.5 Resistance to CDK4/6 inhibitors
- 22.6 Selective degradation of CDK4/6
- 22.7 Other CDK4/6 inhibitors
- 22.8 Conclusion
- Acknowledgments
- References
- Chapter 23. Zanubrutinib: a breakthrough in cancer therapy targeting Bruton’s tyrosine kinase, originating from China, and benefiting the global community
- Abstract
- 23.1 Introduction
- 23.2 Bruton’s tyrosine kinase
- 23.3 Zanubrutinib: drug discovery
- 23.4 Zanubrutinib: clinical trials
- 23.5 Discussion
- References
- Chapter 24. Discovery of FT-2102 (olutasidenib), an inhibitor of mutant isocitrate dehydrogenase 1, for treatment of relapsed or refractory acute myeloid leukemia
- Abstract
- 24.1 Introduction
- 24.2 Main body
- 24.3 Conclusion
- Acknowledgment
- References
- Chapter 25. Ziftomenib (KO-539): a potent and selective Menin inhibitor for the treatment of recurrent or refractory acute myeloid leukemia
- Abstract
- 25.1 Introduction
- 25.2 The discovery of ziftomenib (KO-539)
- 25.3 The discovery stories of other Menin inhibitors
- 25.4 Conclusion
- Acknowledgments
- References
- Chapter 26. Pulrodemstat (CC-90011): a highly potent, selective, and reversible lysine-specific demethylase 1 (LSD1) inhibitor
- Abstract
- 26.1 Introduction
- 26.2 The structure architectures of lysine-specific demethylase 1
- 26.3 The catalytic mechanism of lysine-specific demethylase 1
- 26.4 The biological function of lysine-specific demethylase 1
- 26.5 Lysine-specific demethylase 1-targerd drug discovery
- 26.6 The discovery of pulrodemstat
- 26.7 Clinical trials of pulrodemstat
- 26.8 Conclusions
- Acknowledgments
- References
- Chapter 27. Mavacamten, a first-in-class cardiac myosin inhibitor for the treatment of hypertrophic cardiomyopathy
- Abstract
- 27.1 Introduction
- 27.2 The causes of hypertrophic cardiomyopathy
- 27.3 Mavacamten mode of action
- 27.4 Development of mavacamten
- 27.5 Clinical studies for mavacamten
- 27.6 Deuteration of mavacamten
- 27.7 Other cardiac myosin modulators
- 27.8 Conclusions
- Acknowledgments
- References
- Chapter 28. Verquvo, a first-in-class soluble guanylate cyclase stimulator for the treatment of heart failure
- Abstract
- 28.1 Introduction
- 28.2 Overview of vericiguat
- 28.3 Drug development and synthesis
- 28.4 Preclinical studies and clinical trials
- 28.5 Pharmacokinetic, toxicity properties, and drug interactions
- 28.6 Summary and future perspective
- Rreferences
- Chapter 29. Tafamidis: a transthyretin stabilizer for rare cardiac amyloidosis
- Abstract
- 29.1 Introduction
- 29.2 The structure and related mechanisms of tafamidis
- 29.3 Clinical therapeutics of transthyretin amyloid cardiomyopathy
- 29.4 Summary and prospect
- Funding information
- References
- Chapter 30. Oliceridine (TRV130): a biased agonist of the μ opioid receptor as a novel analgesic
- Abstract
- 30.1 Introduction
- 30.2 Biased signaling of G-protein-coupled receptors
- 30.3 Medicinal chemistry discovery of TRV130
- 30.4 Selectivity and biased pharmacology of TRV130
- 30.5 Preclinical ADMET studies
- 30.6 Preclinical animal efficacy studies
- 30.7 Clinical pharmacokinetic studies
- 30.8 Clinical efficacy studies
- 30.9 Other reported biased µ-opioid receptor agonists
- 30.10 Structural biology study of biased signaling at µ-opioid receptor
- 30.11 Other possible mechanisms for the improved safety profile of TRV130
- 30.12 Summary
- References
- Chapter 31. Sotyktu (Deucravacitinib): the first tyrosine kinase 2 (TYK2) inhibitor approved for the treatment of psoriasis
- Abstract
- 31.1 Introduction
- 31.2 Tyrosine kinase 2 as a popular target in psoriasis
- 31.3 Mechanism of action in Sotyktu
- 31.4 Discovery of Sotyktu
- 31.5 The SARs of Sotyktu as tyrosine kinase 2 JH2 ligands
- 31.6 Pharmacodynamics and pharmacokinetics of Sotyktu
- 31.7 Clinical trials of Sotyktu
- 31.8 Development of Sotyktu derivatives
- 31.9 Conclusion and perspective
- References
- Chapter 32. Bexagliflozin: a sodium-glucose co-transporter-2 inhibitor as anti-diabetic drug derived from phlorizin
- Abstract
- 32.1 Introduction
- 32.2 Sodium-glucose co-transporter-2: a promising target for diabetes treatment
- 32.3 Structural modifications of phlorizin
- 32.4 The production process route for large-scale production of Bexagliflozin
- 32.5 Transitioning from the laboratory to the clinical setting
- 32.6 Conclusion
- References
- Chapter 33. Antidiabetic drugs−targeted PPARγ: from full agonists to selective modulators
- Abstract
- 33.1 Introduction
- 33.2 The discovery of Chiglitazar
- 33.3 Pharmacokinetics evaluation in vitro and in vivo
- 33.4 Perinatal toxicity test in animal
- 33.5 Clinical trials
- 33.6 Ongoing clinical trials
- 33.7 Conclusion
- Acknowledgments
- References
- Chapter 34. Pretomanid: an antibiotic used for the treatment of multidrug-resistant tuberculosis
- Abstract
- 34.1 Introduction
- 34.2 The pathway of designing and development of pretomanid
- 34.3 Pharmacodynamics: mechanism of inhibition
- 34.4 Pharmacokinetics
- 34.5 Chemical synthesis of pretomanid
- 34.6 Pretomanid resistance: mechanism and its emergence
- 34.7 Antimicrobial activity against other bacterial species
- 34.8 Benefits and risks calculations
- 34.9 Conclusion
- Acknowledgment
- References
- Chapter 35. Lecanemab (Leqembi): an amyloid beta monoclonal antibody approved for the treatment of Alzheimer’s disease
- Abstract
- 35.1 Introduction
- 35.2 The research history of Lecanemab
- 35.3 Discussion
- References
- Chapter 36. Pembrolizumab: a breakthrough in cancer immunotherapy
- Abstract
- 36.1 Introduction
- 36.2 Overview of programmed cell death protein-1/programmed cell death protein-L1 pathway
- 36.3 Effects of signaling pathways on programmed cell death protein-1/programmed cell death protein-L1 in cancer
- 36.4 Effects of microRNAs on programmed cell death protein-1/programmed cell death protein-L1 in cancer
- 36.5 Function of programmed cell death protein-1/programmed cell death protein-L1 in cancer
- 36.6 Pembrolizumab
- 36.7 FDA-approved indications (with clinical trial summaries)
- 36.8 Non-small-cell lung cancer
- 36.9 Head and neck squamous cell carcinoma
- 36.10 Renal cell carcinoma
- 36.11 Urothelial carcinoma
- 36.12 FDA-approved indications under accelerated approval (with clinical trial summaries)
- 36.13 Primary mediastinal large B-cell lymphoma
- 36.14 Urothelial carcinoma
- 36.15 Microsatellite instability-high cancer
- 36.16 Gastric cancer
- 36.17 Cervical cancer
- 36.18 Hepatocellular carcinoma
- 36.19 Merkel cell carcinoma
- 36.20 Small cell lung cancer
- 36.21 Non-FDA-approved indications in later-stage clinical trials
- 36.22 Mechanism of action
- 36.23 Conclusion
- References
- Index
- No. of pages: 710
- Language: English
- Edition: 1
- Published: October 18, 2024
- Imprint: Elsevier
- Paperback ISBN: 9780443239328
- eBook ISBN: 9780443239335
BY
Bin Yu
PZ