Polypharmacology in Drug Design and Discovery—Basis for Rational Design of Multitarget Drugs
Zhiguo Wang, Baofeng Yang · 2022
Chapter 3 through Chap. 11 introduces the current status of clinical applications of polypharmacology to disease therapy. This chapter will describe the applications of polypharmacology to drug discovery, mainly from the theoretical account. Specifically, it will explain the theoretical basis for the rational design of new drugs of the “single agent on multiple targets for single disease” category, or the rational design of MTD drugs. Seven essential strategies for MTD drug discovery, including sequence-based epigenetic drugs, sequence-based small-molecule drugs, function-based epigenetic drugs, function-based small-molecule drugs, function-based macromolecule drugs, naturally occurring MTD drugs, and repurposed MTD drugs, will be described in detail with real examples. The contents of this chapter lay the foundation for better understanding of Section II chapters on the methodologies of MTD polypharmacology-based drug discovery and development. Several new concepts on the rational design and discovery of MTDs are proposed by us and presented in this chapter.