New technologies enabling the industrialization of allosteric modulator discovery.

Allosteric modulators (AMs) are a promising avenue towards safe and selective drugs. AMs can interact selectively with unique domains distinct from the endogenous ligand binding site of receptors, up- or downregulating the response to receptor activation. Emphasis is placed in this article on the latest development in high-sensitivity technologies designed to identify AMs of G-protein coupled receptors. In addition to new pharmacological approaches, encouraging results in the crystal resolution of these targets enable use of more rational approaches to identification and optimization of AMs.