Drug-like Properties: Concepts, Structure Design and Methods

1st Edition

from ADME to Toxicity Optimization

Authors: Li Di Edward Kerns
Hardcover ISBN: 9780123695208
eBook ISBN: 9780080557618
Imprint: Academic Press
Published Date: 5th February 2008
Page Count: 552
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Table of Contents

Preface Introductory Concepts 1. Introduction 2. The Advantages of Good Drug-like Properties 3. Barriers to Drug Exposure in Living Systems Physicochemical Properties 4. Rules for Rapid Property Profiling From Structure 5. Lipophilicity 6. pKa 7. Solubility 8. Permeability Disposition, Metabolism and Safety 9. Transporters 10. Blood-Brain Barrier 11. Metabolic Stability 12. Plasma Stability 13. Solution Stability 14. Plasma Protein Binding 15. Cytochrome P450 Inhibition 16. hERG Blocking 17. Toxicity 18. Integrity and Purity 19. Pharmacokinetics 20. Lead-like Compounds 21. Strategies for Integrating Drug-Like Properties Into Drug Discovery Methods 22. Methods for Profiling Drug-like Properties: General Concepts 23. Lipophilicity Methods 24. pKa Methods 25. Solubility Methods 26. Permeability Methods 27. Transporter Methods 28. Blood-Brain Barrier Methods 29. Metabolic Stability Methods 30. Plasma Stability Methods 31. Solution Stability Methods 32. CYP Inhibition Methods 33. Plasma Protein Binding Methods 34. hERG Methods 35. Toxicity Methods 36. Integrity and Purity Methods 37. Pharmacokinetics Methods Specific Topics 38. Diagnosing and Improving Pharmacokinetic Performance 39. Prodrugs 40. Effects of Properties on Biological Assays 41. Formulation Answers to Problems Ap


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.


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© Academic Press 2008
Academic Press
eBook ISBN:
Hardcover ISBN:


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

About the Authors

Li Di Author

Li Di is an Associate Research Fellow at Pfizer, USA

Affiliations and Expertise

Pfizer, East Lyme, CT, USA

Edward Kerns Author

Affiliations and Expertise

National Institutes of Health, Bethesda, MD, USA