PBI-4050 acts as an agonist for GPR40 and as an antagonist or inverse agonist for GPR84.
PBI-4050, a synthetic analogue of a medium-chain length fatty acid, binds to FFA receptor 1 (FFAR1/GPR40) and GPR84. To determine the potential role of PBI-4050 on diabetic kidney disease, The accelerated model of type 2 diabetic nephropathy, eNOS-/- db/db mice are utilized. Mice are treated with either vehicle or PBI-4050 (100 mg/kg) by daily gavage from 8-20 weeks of age. eNOS-/- db/db mice are moderately hypertensive, and PBI-4050 has no effect on blood pressure. Furthermore, compared with vehicle-treated mice, which exhibit a decrease in glomerular filtration rate (GFR) from 8-20 weeks, PBI-4050 preserves GFR. Podocyte number per glomerulus section markedly decreases from 8-20 weeks of age in vehicle-treated mice, while PBI-4050 treatment significantly slows this loss[1].
[1]. Li Y, et al. Fatty acid receptor modulator PBI-4050 inhibits kidney fibrosis and improves glycemic control. JCI Insight. 2018 May 17;3(10). pii: 120365.