Carmegliptin

Carmegliptin (RO-4876904) is an orally active and potent DPP IV inhibitor with a human DPP IV IC₅₀ of 6.8 nM. Carmegliptin binds to the S1 pocket of DPP IV, blocks the degradation of GLP 1, potentiates endogenous GLP 1, increases plasma insulin levels, alleviates hyperglycemia, improves glucose tolerance. Carmegliptin acts as a substrate for human P glycoprotein without inhibiting the transporter, shows low in vitro cell permeability. Carmegliptin can be used for the research of type 2 diabetes, non insulin dependent diabetes mellitus^[1][2][3]. In Vitro:Carmegliptin potently inhibits human DPP-IV with an IC₅₀ of 6.8 nM^[1].
Carmegliptin (10 μM) is highly selective for human DPP-IV, with no significant off-target activity at 10 μM and > 100-fold selectivity over related proline-specific dipeptidyl peptidases^[1].
Carmegliptin does not inhibit or induce CYP450 enzymes^[1]. In Vivo:Carmegliptin (0.3 mg/kg; p.o.; single dose) reduces glucose excursion by 66% in insulin-resistant Zucker fatty (fa/fa) rats 40 minutes after an oral glucose challenge^[1].
Carmegliptin (20 mg/kg; p.o.; daily; 7 days) improves insulin sensitivity via increased GIR and shows a trend toward reduced hepatic glucose production in insulin-resistant Zucker fatty (fa/fa) rats^[1].
Carmegliptin (10 mg/kg; p.o.; single dose) produces a significant reduction in fasting blood glucose and reduces the oral glucose tolerance test AUC_0-t by 30%^[1].
Carmegliptin(3 mg/kg; p.o.; single dose) produces sustained plasma DPP-IV inhibition in non-diabetic cynomolgus monkeys, with 40% and 60% baseline activity remaining at 24 and 48 hours post-administration^[1].