Abstract
GPCRs remain the most important drug target comprising ~ 34% of the Food and Drug Administration (FDA)-approved drugs. In modern pharmacology of GPCRs, modulating receptor signaling based on requirement of a specific disorder is of immense interest. Classical drugs targeting orthosteric sites in GPCRs completely block the binding of endogenous ligand and consequently inhibit all important signals from a GPCR. Some of many signals elicited by the endogenous ligands may play vital role and inhibiting these may also cause severe side effects in the long run. However, allosteric drugs can modulate GPCR signaling without blocking the endogenous ligand binding. Therefore, allosteric drugs can maintain beneficial signaling of the receptor and prevent unwanted side effects. In this chapter, we will discuss GPCR crystal structures solved with allosteric ligands, advantages of allosteric drugs, and allosteric drugs which are in clinical use or trials.