Protein Homeostasis in Drug Discovery A Chemical Biology Perspective

by Kostic, Milka; Jones, Lyn H.

• ISBN13: 9781119774129
• ISBN10: 1119774128
• Edition: 1st
• Format: Hardcover
• Copyright: 2022-12-08
• Publisher: Wiley

Summary

Protein Homeostasis in Drug Discovery

Comprehensive resource on all aspects of protein homeostasis, covering both historical perspectives and emerging technologies that are revolutionizing the field

Protein Homeostasis in Drug Discovery highlights drug discovery and development efforts targeting protein homeostasis and considers the emerging appreciation that a protein’s activity may not be the only factor to consider when developing therapeutic agents.

The chapters cover various aspects of protein homeostasis such as cellular localization, abundance, interactions, and more. Moreover, the text contains up-to-date information regarding targeted protein degradation, an emerging drug discovery modality.

Readers interested in targeting different regulatory events that control protein homeostasis or modulating protein abundance will find this book an excellent resource. Furthermore, those interested in the link between biological function and regulating protein levels in living organisms, especially in the context of drug discovery, will learn from numerous examples discussed in this book.

In Protein Homeostasis in Drug Discovery, readers can expect to find information on:

• Protein folding, quality control, pharmacology, and drug targeting processes
• Recent advances in our understanding of protein homeostasis, covering emerging technologies and opportunities for therapeutic intervention
• Targeted protein degradation (TPD) and strategies such as PROTACs and molecular glues, including a chapter on TPD as an antiviral drug discovery strategy
• Drug discovery and development efforts aimed at correcting, stabilizing, and rescuing proteins, with examples included
• Advantages and key shortcomings of both phenotypic and target-based traditional drug discovery methods

Collectively, Protein Homeostasis in Drug Discovery offers the reader an opportunity to learn more about the importance of considering and targeting protein homeostasis. The text is a must-read resource for academics, professionals in the pharmaceutical industry, and advanced students in various science-related fields.

Author Biography

Milka Kostic, PhD, is the Program Director for Chemical Biology at the Dana-Farber Cancer Institute and her interests include advocating for the importance of chemical biology as a critical link in the chemistry-biology-medicine continuum.

Lyn H. Jones, PhD, is currently Director of the Center for Protein Degradation at the Dana-Farber Cancer Institute and his interests include using chemogenomics and chemoproteomics to advance new therapeutic modalities.

Table of Contents

SECTION I  Protein Folding and Quality Control in Drug Discovery

 

Chapter – 1 :  Epichaperomes as a gateway to understanding, diagnosing, and treating disease through rebalancing protein-protein interaction networks

Chander S. Digwal, Sahil Sharma, Anand R. Santhaseela, Stephen D. Ginsberg, and Gabriela Chiosis,

Chapter – 2 :  Stability of Steroid Hormone Receptors: The Intersection of Proteostasis and Selective Degradation

Zachary J. Gale-Day and Jason E. Gestwicki

Chapter – 3: Pharmacological Chaperones; therapeutic potential for diseases resulting from GPCR misfolding

Suli-Anne Laurin, Sajjad Ahrari, and Michel Bouvier

 

SECTION II: Protein Degradation and Clearance as Drug Targeting Opportunities

 

Chapter – 4: Exploiting the proteasome for disease treatment: from dynamic architecture to vast functions

Gwen R. Buel, Xiuxiu Lu, and Kylie J. Walters

Chapter – 5: Targeting the ubiquitination cascade for drug discovery

Qi Liu, Gabriel  LaPlante, and Wei Zhang

Chapter – 6: Understanding, targeting and hijacking autophagy

Hongguang Xia, Xiaoyan Xu, Mengxin Zhou, Manke Zhang, and Lingzhi Ye,

Chapter – 7: Deubiquitinating enzymes: from undruggable targets to emerging opportunities

Ariana Jones, Xiaoxi Liu, Anthony Varca, Lara Doherty, and Sara Buhrlage

 

SECTION III:  Redirecting Protein Degradation Processes for Drug Development

 

Chapter – 8: History of IMiDs and protein degradation as a pharmacological modality

Junichi Yamamoto, Tomoko Asatsuma-Okumura, Takumi Ito, Yuki Yamaguchi, and Hiroshi Handa

Chapter – 9: PROTAC Degraders: Mechanism, Recent Advances and Future Challenges

Alessio Ciulli and Oliver Hsia

Chapter – 10: Biochemical principles of targeted protein degradation

Roman V. Agafonov, Richard W. Deibler, W. Austin Elam, Joe Sahil Patel, and Stewart L. Fisher

Chapter – 11: Pharmacology of PROTAC degrader molecules: optimizing for in vivo performance

Andy Pike, Sofia Guzzetti, Pablo Morentin Gutierrez, and James S. Scott

 

SECTION IV:  Emerging technologies and future opportunities

 

Chapter – 12: Proximity-inducing bifunctional molecules beyond PROTACs

Sophia Lai, Ashley E. Modell, and Amit Choudhary

Chapter – 13: Strategies for tag-based protein control

Behnam Nabet, Nathanael S. Gray, and Fleur M. Ferguson

Chapter – 14: Targeted protein degradation in antiviral drug discovery

Mélissanne de Wispelaere and Priscilla L. Yang

Chapter – 15:  Beyond Inhibition: Ligand-Based Pharmacological Exploration as a Strategy Towards New Targets and Modalities

Milka Kostic and Lyn H. Jones