Drug-like Properties: Concepts, Structure Design and Methods

from ADME to Toxicity Optimization


  • Li Di, Pfizer, East Lyme, CT, USA
  • Edward Kerns, National Institutes of Health, Bethesda, MD, USA

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.
View full description


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.


Book information

  • Published: February 2008
  • ISBN: 978-0-12-369520-8


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 chapter on pharmacokinetics provides a very good overview of the topic. This book is well worth the purchase price." --Walter Korfmacher, NJ, USA

Table of Contents

PrefaceIntroductory Concepts1. Introduction2. The Advantages of Good Drug-like Properties3. Barriers to Drug Exposure in Living SystemsPhysicochemical Properties4. Rules for Rapid Property Profiling From Structure5. Lipophilicity6. pKa7. Solubility8. PermeabilityDisposition, Metabolism and Safety9. Transporters10. Blood-Brain Barrier11. Metabolic Stability12. Plasma Stability13. Solution Stability14. Plasma Protein Binding15. Cytochrome P450 Inhibition16. hERG Blocking17. Toxicity18. Integrity and Purity19. Pharmacokinetics20. Lead-like Compounds21. Strategies for Integrating Drug-Like Properties Into Drug DiscoveryMethods22. Methods for Profiling Drug-like Properties: General Concepts23. Lipophilicity Methods24. pKa Methods25. Solubility Methods26. Permeability Methods27. Transporter Methods28. Blood-Brain Barrier Methods29. Metabolic Stability Methods30. Plasma Stability Methods31. Solution Stability Methods32. CYP Inhibition Methods33. Plasma Protein Binding Methods34. hERG Methods35. Toxicity Methods36. Integrity and Purity Methods37. Pharmacokinetics MethodsSpecific Topics38. Diagnosing and Improving Pharmacokinetic Performance39. Prodrugs40. Effects of Properties on Biological Assays41. FormulationAnswers to ProblemsAppendix I: General ReferencesAppendix II: Glossary