Evaluation of the Biological Activity of Compounds: Techniques and Mechanism of Action Studies

Dougall, I. C,  Unitt, J.


The first step in the biological assessment of compounds synthesized by medicinal chemists usually involves testing in a range of in vitro biochemical/pharmacological assays. The primary purpose of these experiments is to generate robust estimates of drug properties including potency, affinity, intrinsic activity, or efficacy, as well as providing an understanding of the mechanism of action of the compounds. This information is used by medicinal chemists to generate structure activity relationships that drive the optimization of compounds appropriate for testing in more complex in vitro, ex vivo, and ultimately in vivo assays. This chapter outlines the biological systems typically used in modern drug discovery programs, describing the measurements made and highlighting the properties of various different classes of drugs and the principles underlying their analysis. The subsequent testing and analysis of compounds in animal models is also described, and the utility of such models for predicting efficacy, “dose-to-man,” and safety issues is discussed.

Ref: The Practice of Medicinal Chemistry (Fourth Edition), Chapter 2, 2015, Pages 15–43.