3. COVALENT ENZYME INHIBITION IN DRUG DISCOVERY AND DEVELOPMENT

  1. Hsiu-Chiung Yang2,
  2. Wu-Kuang Yeh3 and
  3. James R. McCarthy4
  1. Shujaath Mehdi

Published Online: 6 DEC 2013

DOI: 10.1002/9781118739907.ch3

Enzyme Technologies: Pluripotent Players in Discovering Therapeutic Agents

Enzyme Technologies: Pluripotent Players in Discovering Therapeutic Agents

How to Cite

Mehdi, S. (2013) COVALENT ENZYME INHIBITION IN DRUG DISCOVERY AND DEVELOPMENT, in Enzyme Technologies: Pluripotent Players in Discovering Therapeutic Agents (eds H.-C. Yang, W.-K. Yeh and J. R. McCarthy), John Wiley & Sons, Inc, Hoboken, NJ. doi: 10.1002/9781118739907.ch3

Editor Information

  1. 2

    Eli Lilly and Company, Indianapolis, Indiana

  2. 3

    Indiana University Purdue University Indianapolis, Indianapolis, Indiana

  3. 4

    Indiana University Purdue University Indianapolis, Indianapolis, Indiana

Author Information

  1. Immunoinflammation Therapeutic Strategy Unit, Sanofi Pharmaceuticals, Bridgewater, New Jersey

Publication History

  1. Published Online: 6 DEC 2013
  2. Published Print: 30 DEC 2013

ISBN Information

Print ISBN: 9780470286265

Online ISBN: 9781118739907

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Keywords:

  • covalent enzyme inhibition;
  • covalent inhibitors;
  • drug discovery;
  • irreversible inhibitors;
  • pseudo-irreversible inhibition;
  • slow-binding inhibitors

Summary

In this chapter, a perspective is given on covalent inhibitors, which in general fall in the middle and to the right in the continuum - that is, that are slowly reversible or fully irreversible. The chapter discusses the use of irreversible inhibitors that have also been very useful as tools for target or pathway validation, for target discovery, or for establishing the selectivity of reversible inhibitors. Different types of inhibitors from the point of view of inhibition concept or inhibition principle are discussed. The chapter talks about conceptual and practical aspects of the kinetics of slow binding and of irreversible inhibitors. It provides specific examples of inhibitors classed by type of covalent attachment. The chapter ends with a discussion on special topics relating to irreversible inhibition and with guidelines that may help in decision-making when encountering irreversible inhibition in a project.