PBI-4050 (sodium salt)

PBI-4050 is an agonist of free fatty acid receptor 1 (FFAR1/GPR40) and an antagonist of G protein-coupled receptor 84 (GPR84). It induces beta-arrestin-2 recruitment in a reporter assay using HEK293 cells expressing human FFAR1/GPR40 (EC50 = 275 µM). PBI-4050 inhibits activation of GPR84 induced by decanoic acid (Cay-20838) or embelin (Cay-11838) in reporter assays using HEK293 cells expressing the human receptor (IC50s = 398 and 209 µM, respectively). In vivo, PBI-4050 (200 mg/kg) decreases renal histological lesion scores in a mouse model of doxorubicin-induced nephrotoxicity. It also reduces tissue fibrosis in several additional in vivo rodent models, including carbon tetrachloride-induced hepatotoxicity and bleomycin-induced pulmonary fibrosis. PBI-4050 (100 mg/kg) decreases albuminuria, prevents decreases in the glomerular filtration rate (GFR) and podocyte numbers, and reduces blood glucose levels in a model of accelerated type 2 diabetes using eNos-/- db/db mice.. Solulibility: DMSO: Sparingly soluble: 1-10 mg/ml: Ethanol: Sparingly soluble: 1-10 mg/ml, PBS (pH 7.2): Sparingly soluble: 1-10 mg/ml.