Setogepram (PBI-4050) acts as an orally active agonist for GPR40 and as an antagonist or inverse agonist for GPR84^[1]. Setogepram (PBI-4050) decreases renal, liver and pancreatic fibrosis^[1][2]. Setogepram (PBI-4050) exerts anti-fibrotic, anti-inflammatory and anti-proliferative actions^[2]. IC50 & Target: GPR40, GPR84^[1] In Vitro: Setogepram (PBI-4050; 500 µM; 24 hours) inhibits TGF-β (10 ng/mL)-activated human hepatic stellate cells (HSCs) proliferation^[2].
Setogepram (PBI-4050; 250 or 500 µM; 24hours) dose-dependently arrests HSCs at the G0/G1 phase without inducing apoptosis^[2]. In Vivo: Setogepram (PBI-4050; 100 mg/kg/day; gavage from 8-20 weeks of age) markedly decreases hyperglycemia and markedly improvea glucose tolerance in type 2 diabetes eNOS^-/-db/db mice^[1].