FOXO1-IN-3 is a highly-selective, orally active inhibitor of FOXO1 that reduces hepatic glucose production and improves insulin sensitivity and glucose regulation in db/db mice, without causing weight gain [1].

FOXO1-IN-3 (Compound 10) at 10 μM inhibits cAMP/Dexamethasone-induced mRNA expression of G6pc and Pck1 in primary hepatocytes from normal mice after 6 hours of treatment [1].

FOXO1-IN-3 (Compound 10) (16 mg/kg, oral administration, twice daily for 10 days) effectively reduced blood glucose levels in db/db mice [1]. Additionally, it showed synergistic glucose-lowering effects in Streptozotocin-induced diabetic mice with depleted β-cells when combined with FGF21 (0.45 mg/kg) [1]. FOXO1-IN-3 exhibited significant plasma exposure and oral bioavailability in mice at 1 mg/kg intravenously and 10 mg/kg orally, despite a short half-life [1].