Receptor Targets in Drug Discovery

Receptors, located on both the cell surface and within the cell are the defined molecular targets through which drugs produce their beneficial effects in various disease states. Initially conceptualized over a century ago by Ehrlich and Langley, receptor concepts and receptor theory have undergone continuous modification as their behavior in normal and disease states/tissues have been more clearly characterized. Since the isolation of the nicotinic acetylcholine receptor (nAChR) from the Torpedo , some 50 years ago, new techniques of molecular biology have made it relatively routine to isolate receptors, including orphan receptors. Once these have been validated, they can be used in conjunction with high- throughput screening approaches to identify “hits,” molecules that bind with relatively high affinity to these targets. Such hits can then be optimized to druglike entities using combinatorial/parallel synthesis technology platforms to yield clinical candidates that are potent, efficacious, and bioavailable entities with appropriate safety profiles. Keywords: Agonist; Antagonist; Drug; G-protein–Coupled Receptors; Heterotrimeric G-protein; High-throughput Screening; Ion Channels; Ligand; New Chemical Entity (NCE); Orphan Receptor; Receptor; SAR; Therapeutic Index