Drug-like Properties: Concepts, Structure Design and Methods

1st Edition

from ADME to Toxicity Optimization

Authors: Li Di Edward Kerns
Print ISBN: 9780124054486
eBook ISBN: 9780080557618
Imprint: Academic Press
Published Date: 5th February 2008
Page Count: 552
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Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process.

The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties.

Key Features

  • Serves as an essential working handbook aimed at scientists and students in medicinal chemistry
  • Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies
  • Discusses improvements in pharmacokinetics from a practical chemist's standpoint


Medicinal chemists in private industry, research centers and government labs; ADME scientists who develop assays and perform measurements, as well as instrument vendors and software companies in this area; and students in medicinal chemistry and pharmaceutical sciences.

Table of Contents


Introductory Concepts

  1. Introduction
  2. The Advantages of Good Drug-like Properties
  3. Barriers to Drug Exposure in Living Systems

Physicochemical Properties

  1. Rules for Rapid Property Profiling From Structure
  2. Lipophilicity
  3. pKa
  4. Solubility
  5. Permeability

Disposition, Metabolism and Safety

  1. Transporters
  2. Blood-Brain Barrier
  3. Metabolic Stability
  4. Plasma Stability
  5. Solution Stability
  6. Plasma Protein Binding
  7. Cytochrome P450 Inhibition
  8. hERG Blocking
  9. Toxicity
  10. Integrity and Purity
  11. Pharmacokinetics
  12. Lead-like Compounds
  13. Strategies for Integrating Drug-Like Properties Into Drug Discovery


  1. Methods for Profiling Drug-like Properties: General Concepts
  2. Lipophilicity Methods
  3. pKa Methods
  4. Solubility Methods
  5. Permeability Methods
  6. Transporter Methods
  7. Blood-Brain Barrier Methods
  8. Metabolic Stability Methods
  9. Plasma Stability Methods
  10. Solution Stability Methods
  11. CYP Inhibition Methods
  12. Plasma Protein Binding Methods
  13. hERG Methods
  14. Toxicity Methods
  15. Integrity and Purity Methods
  16. Pharmacokinetics Methods

Specific Topics

  1. Diagnosing and Improving Pharmacokinetic Performance
  2. Prodrugs
  3. Effects of Properties on Biological Assays
  4. Formulation

Answers to Problems Ap


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About the Author

Li Di

Li Di is an Associate Research Fellow at Pfizer, USA

Affiliations and Expertise

Pfizer, East Lyme, CT, USA

Edward Kerns

Affiliations and Expertise

National Institutes of Health, Bethesda, MD, USA


JOURNAL OF MEDICINAL CHEMISTRY, OCTOBER 2008: "The authors do an excellent job of providing insight into the background of the many factors that influence drug-like properties...[This] easy-to-read text is...an excellent addition to the library of practicing medicinal chemists and of graduate students in the pharmaceutical sciences. It provides a wealth of information for a reasonable price."--Thomas E. Prisinzano, Dept. of Medicinal Chemistry, University of Kansas, KS, USA DOODY’S, SEPTEMBER 2008: “This is a valuable reference for any scientist who works as part of a drug discovery team and especially those who are involved in ADME to toxicity optimization […] The authors have done a nice job of presenting this information in a concise, readable format.”--Thomas Pazdernik, University of Kansas Medical Center, KS, USA “[Recently] I bought your excellent book, and I want to congratulate you and thank you for injecting life into the science of ADMET, lifting the subject to ‘bestseller,’ enjoyable reading material. It is the best book that I have come across that makes a great job of fostering collaborative interactions between ADMET and Medicinal Chemistry scientists in advancing strategies of drug discovery.”--Dr. Collen Masimirembwa, Chief Scientific Officer, AiBST "I am very impressed...[The book] is destined to become an authoritative text on the whole topic area of drug-like molecules and ADME screening. The chapters are well written and include sufficient detail and references so that the reader can make use of the information effectively. The book could be used in a graduate-level course for medicinal chemists or DMPK scientists. The book would also be very helpful for scientists working in one area of DMPK who wish to become DMPK project managers and need to increase their understanding of other areas of DMPK that are outside of their own specific expertise function. The chapte