tcsc0282 Fasiglifam

Fasiglifam (TAK-875) is a potent, selective and orally bioavailable GPR40 agonist with EC₅₀ of 72 nM.

IC50 & Target: EC50: 72 nM (GPR40)

In Vitro: Fasiglifam (TAK-875) (0.01-10 μM) produces a concentration-dependent increase in intracellular IP production in CHO-hGPR40, with EC₅₀ of 0.072 μM. Fasiglifam (TAK-875) (0.1-10 μM) dose-dependently augments intracellular IP production in CHO cells^[1]. Fasiglifam (TAK-875) (3-30 μM) concentration-dependently augments [Ca²⁺]_i. In the presence of 10 mM glucose, TAK-875 (0.001-10 μM) dose-dependently stimulats insulin secretion from INS-1 833/15 cells^[2].

In Vivo: Fasiglifam (TAK-875) (10 mg/kg, p.o.) increases plasma insulin levels in ZDF rats. Fasiglifam (TAK-875) (30 mg/kg, p.o.) improves fasting hyperglycemia without affecting fasting normoglycemia. Fasiglifam (TAK-875) at 30 mg/kg, which is a 3- to 10-fold higher dose compared with the dose that improved glucose tolerance in diabetic rats, does not alter fasting glucose levels in SD rats with normal glucose homeostasis. Likewise, Fasiglifam (TAK-875) does not significantly alter insulin secretion in SD rats with normal fasting glucose levels ^[1].