GW9508

Использование

GW9508 is a GPR40 full agonist, used to regulate glucose in rats. Can be applied to the treatment of diabetes type 2. GPR120 selective and potent agonist also used in the treatment of diabetes type 2 due to GPR120’s ability to mediate GLP-1 secretion, insulin sensitization and anti-obesity effects.

Биологическая активность

Potent and selective agonist for the free fatty acid receptor FFA 1 (GPR40) (pEC 50 values are 7.32, < 4.3 and < 4.3 for FFA 1 , FFA 2 and FFA 3 receptors respectively). Inactive against a range of other GPCRs, kinases, proteases, integrins and PPARs. Potentiates glucose-stimulated insulin secretion in MIN6 cells (pEC 50 = 6.14).

Биохимия/физиол Действия

GW9508 is a selective FFA1/GPR40 agonist. GPR40 was formerly an orphan G protein-coupled receptor whose endogenous ligands have now been identified as free fatty acids (FFAs). The receptor, named FFA receptor 1, has been implicated in the pathophysiology of type 2 diabetes and is a drug target because of its role in FFA-mediated enhancement of glucose-stimulated insulin release. GW9508 showed greater than 500-fold selectivity for GPR40 over GPR41 and GPR43 and possessed a good in vitro and in vivo profile with excellent bioavailability. GW9508 stimulated intracellular Ca2+ mobilization in human embryonic kidney HEK-293 cells expressing GPR40 or GPR120, but not in the parent HEK-293 cell line. GW9508 dose dependently potentiated glucose-stimulated insulin secretion in MIN6 cells, but not in primary rat or mouse islets. GW9508 potentiates the KCl-mediated increase in insulin secretion in MIN6 cells.