GPCR-targeted drug discovery

G-protein coupled receptors (GPCRs), also known as 7 transmembrane receptors, are the largest family of cell surface receptors. They are involved in a wide variety of physiological and pathological processes and are the largest family of druggable targets. Our group is interested in the biological functions of GPCRs and their roles in major diseases including autoimmune disease, neurodegenerative diseases, metabolic diseases and etc. In addition to the mechanism study, we also screen and develop drugs targeting GPCRs. Natural compounds may exert their effect by targeting GPCRs.

For example, Herbal-based food supplement is widely used to treat obesity. Among them, the Hoodia gordonii (Asclepiadaceae) supplements are extremely popular. The African cactiform has been used for thousands of years by Xhomani Bushmen as an anorexant during hunting trips and has been proposed as a new agent for the management of body weight. However, the true active components and molecular targets of Hoodia remain unclear. We have demonstrated that Gordonoside F, a steroid glycoside isolated from Hoodia gordonii, but not the widely known P57, activates specifically GPR119, a receptor critically involved in metabolic homeostasis, and leads to increased insulin secretion and reduced food intake. These results not only demonstrate that the activation of GPR119 receptor is an important mechanism underlying Hoodia gordonii’s therapeutic effect, but also suggest that Gordonoside F or its congeners could be developed into new drugs in treating metabolic disorders.