Enzymology in Drug Discovery

Erscheinungsjahr 2026
ISBN: 978-0-443-52162-1
Verlag: Elsevier Science & Technology

Buch, Englisch, Format (B × H): 152 mm x 229 mm

This volume is focused on the application of enzymology to drug discovery, with the overarching objective of introducing the general audience to the important role that enzymology plays in modern, molecular targeted drug discovery. The volume opens with a chapter on the role of enzymes in normal human physiology and the causal role played by aberrant enzyme activity in various disease state. A second chapter provides a comprehensive review of inhibition modalities for therapeutic enzyme inhibitors. From there the volume is composed of chapters that cover two general categories of information: (1) methodologies for studying enzyme-ligand interactions and (2) case studies of molecular targeted drug discovery against specific enzyme targets. Chapters within the first category cover methods such as assay design, the role of structural biology in drug optimization, analysis of slow and tight binding inhibitors, enzyme-inhibitor complex dynamics, and covalent enzyme inactivators. The second category includes case studies of therapeutic inhibitors of various enzyme target classes: proteases, methyltransferases, histone demethylases, helicases, nucleic acid processing enzymes, kinesin motor proteins, and cytochrome P450s. Finally, a chapter is also devoted to therapeutic replacement or repair of defective enzymes.

Autoren/Hrsg.

Weitere Mitwirkende

Christianson, David

Allen, Karen N.

Copeland, Robert

Fachgebiete

• Naturwissenschaften Biowissenschaften Biochemie (nichtmedizinisch)
• Naturwissenschaften Physik Angewandte Physik Biophysik
• Naturwissenschaften Biowissenschaften Molekularbiologie

Inhaltsverzeichnis

1. Molecules of Life: The Critical Role of Enzymes in Health and Disease
Rachel Grimley
2. Inhibition Modalities for Therapeutic Enzyme Inhibitors
Shane M. Buker
3. Assay Design for Enzyme Targets in Drug Discovery: From Hit Identification to Lead Optimization
Charlene Bashore
4. Covalent Hit Discovery and Characterization by Label-Free Approaches
Bharath Srinivasan
5. Slow and Tight-Binding Enzyme Inhibition
Peter Tonge
6. Structure-based drug discovery of enzyme-inhibitor complexes using protein X-ray crystallography
Margarita Tararina, Nicolas Szapiel, Max Ruzanov and Kevin Kish
7. High-Throughput Evaluation of Enzyme Inhibition Dynamics
Amaury Fernandez
8. Protease inhibitors as therapeutics
Tom Meek
9. Experimental Methods for Detecting Methyltransferase Activity and Characterization of Inhibitors
Aravind Basavapathruni and Zachary Gurard-Levin
10. Experimental Approaches to Histone Demethylase Biology: Purification, Detection and Functional Readouts
Johnathan Whetstine
11. DNA and RNA helicase inhibitors as therapeutics
Jennifer Castro
12. Inhibitors of nucleic acid processing as therapeutics
Israel Canadas, Yaiza Jimenez and Takahiko Murayama
13. Mechanistic Characterization of Heterbifunctional Modalities Using Biochemical Methods
Argyrides Argyrou
14. Proximity Detection Assays for Identifying and Characterizing Molecular Glues of Target Proteins and E3 Ligases
Tim Wigle
15. Structural Biology of the Axon Degeneration Executioner SARM1: Insights into Regulation, Enzymology and Inhibition
Robert Hughes
16. Kinesin motor protein inhibitors as therapeutics
Maureen Lynes and Brian Andrew Sparling
17. Beyond PARP1: Enzymology, Biology and Therapeutic Targeting of PARPs 4–16
Tim J. Mitchison
18. Drug Metabolism and Disposition: The Role of Metabolic Enzymes
Benjamin Barlock and Rohitash Jamwal
19. Utilization of In Vitro Assays for CYP Inhibition and Induction to Enable Clinical Drug-Drug Interaction Risk Assessment
Nigel J. Waters and Panos Hatsis
20. Methods to Create Therapeutics by Replacing or Repairing Defective Enzymes
Charles Albright

Über Autor(innen)

Copeland, Robert
Robert A. Copeland is a prominent biomedical sciences entrepreneur and executive, with a strong track record of starting, building and leading successful drug discovery organizations. He is widely recognized for his pioneering contributions to precision medicine, enzymology, and oncology drug discovery. Copeland has contributed to the discovery of 21 investigational new drugs that have transitioned to the clinic, five of which are FDA-approved medicines. He has contributed over 200 publications to the scientific literature, holds 14 issued U.S. patents and has authored seven highly acclaimed texts books in the areas of protein sciences, enzymology and drug discovery. He is currently Venture Partner at Altas Venture, an Advisor to Google Ventures, and Adjunct Professor at the Perelman School of Medicine, The University of Pennsylvania. Beyond his career, he is an avid cyclist, bass fisherman and a second-degree black belt in judo, a sport in which he continues to actively participate.

Christianson, David
After completing studies for the A.B., A.M., and Ph.D. degrees in chemistry at Harvard University, David W. Christianson joined the faculty of the University of Pennsylvania, where he is currently the Roy and Diana Vagelos Professor in Chemistry and Chemical Biology. At Penn, Christianson’s research focuses on the structural and chemical biology of the zinc-dependent histone deacetylases as well as enzymes of terpene biosynthesis. His research accomplishments have been recognized by several awards, including the Pfizer Award in Enzyme Chemistry and the Repligen Award in Chemistry of Biological Processes from the American Chemical Society, a Guggenheim Fellowship, and the Elizabeth S. and Richard M. Cashin Fellowship from the Radcliffe Institute for Advanced Study at Harvard University. Christianson is also a dedicated classroom teacher, and his accomplishments in this regard have been recognized by the Lindback Award for Distinguished Teaching at Penn and a Rhodes Trust Inspirational Educator Award from Oxford University. Christianson has also held visiting professorships in the Department of Biochemistry at Cambridge University and the Department of Chemistry and Chemical Biology at Harvard University. Christianson has served with Prof. Anna Pyle as Co-Editor-in-Chief of Methods in Enzymology since 2015.

Allen, Karen N.
Dr. Karen N. Allen works at the Department of Chemistry of the Boston University, the Metcalf Center for Science and Engineering