Carmegliptin hydrochloride  (Synonyms: RO-4876904 hydrochloride)

Carmegliptin hydrochloride (RO-4876904 hydrochloride) is an orally active and potent DPP‑IV inhibitor with a human DPP‑IV IC₅₀ of 6.8 nM. Carmegliptin hydrochloride 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 hydrochloride acts as a substrate for human P‑glycoprotein without inhibiting the transporter, shows low in vitro cell permeability. Carmegliptin hydrochloride can be used for the research of type 2 diabetes, non‑insulin‑dependent diabetes mellitus^[1][2][3].

Carmegliptin hydrochloride potently inhibits human DPP-IV with an IC₅₀ of 6.8 nM^[1].
Carmegliptin (10 μM) hydrochloride 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 hydrochloride does not inhibit or induce CYP450 enzymes in vitro^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Carmegliptin (0.3 mg/kg; p.o.; single dose) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

450.37

C₂₀H₃₀Cl₂FN₃O₃

813452-14-1

COC1=C(OC)C=C2CCN(C[C@H](N3C[C@H](CC3=O)CF)[C@H](C4)N)[C@]4([H])C2=C1.Cl.Cl

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Mattei P, et al. Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg Med Chem Lett. 2010;20(3):1109-1113.  [Content Brief]

  [2]. Boehringer M, et al. (Hoffmann La Roche Inc). United States, US20040259903A1. 2004-12-23.

  [3]. Kuhlmann O, et al. Interaction potential of Carmegliptin with P-glycoprotein (Pgp) transporter in healthy volunteers. J Drug Assess. 2014;3(1):28-37. Published 2014 Mar 3.  [Content Brief]