Drug Discovery

Abstract

Historically, many pharmaceutical agents were naturally occurring chemical substances, and discovery of their medicinally beneficial properties was serendipitous rather than deliberate. In the last several decades, research scientists have evaluated many molecules in a systematic manner and discovered drug molecules with interesting pharmacological characteristics. It was quite possible that hundreds (if not thousands) of potential drug candidate molecules would be made and tested for pharmacodynamic action in what was a very laborious process. Natural products and synthetic organic products, both of which are small molecules, were the typical drugs brought to market. The development of cholesterol-lowering drugs illustrates this research and development (R&D) model. The plasma cholesterol-lowering drug mevastatin is a drug derived from natural products. It is a fungal metabolite and one of the “statins” that lowers cholesterol by inhibiting the enzyme human growth hormone coenzyme A (HMG CoA) reductase.

Once the drug molecule enters the microenvironment of the target receptor, it is necessary that the three-dimensional geometry of the molecule precisely matches the three-dimensional geometry of the receptor’s active site to affect a response.