Chemokine receptor antagonists from discovery to the clinic.

Abstract

Chemokine receptors belong to one of the most pharmacologically exploited proteins; the G-protein coupled receptors (GPCRs). Drugs that target these receptors make up greater than 45% of all known marketed medicines. The first recorded uses of drugs directed at this important family of proteins can be traced back to ancient Chinese and Indian physicians who were using plant extracts to treat a variety of disorders (Ding 1987; Sevenet 1991). For example, although tetrahydropalmitine, a potent dopamine receptor antagonist, was isolated only a few years ago from the fumewort plant, the plant itself was first described for its tranquilizing effects as early as the fifth century (Ding 1987). Extracts from the deadly nightshade family have been widely used as analgesics and anesthetics in medicine since ancient times (Ding 1987). The active principles, identified as the alkaloids atropine and scopolamine, are potent musacarinic receptor antagonists.