Carmegliptin (hydrochloride)  (Synonyms: RO-4876904 (hydrochloride))

Carmegliptin (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) 可强效抑制人源 DPP-IV，其 IC₅₀ 为 6.8 nM^[1]。
Carmegliptin (10 μM) (hydrochloride) 对人源 DPP-IV 具有高度选择性，在 10 μM 浓度下无显著脱靶活性，且对相关脯氨酸特异性二肽基肽酶的选择性超过 100 倍^[1]。
Carmegliptin (hydrochloride) 不会在体外抑制或诱导 CYP450 酶^[1]。

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

Carmegliptin (0.3 mg/kg；口服；单次给药) (hydrochloride) 可在口服葡萄糖负荷 40 分钟后，使胰岛素抵抗型 Zucker 肥胖 (fa/fa) 大鼠的血糖波动降低 66%^[1]。
Carmegliptin (20 mg/kg；口服；每日一次；连续 7 天) (hydrochloride) 可通过提升 GIR 改善胰岛素敏感性，并且在胰岛素抵抗型 Zucker 肥胖 (fa/fa) 大鼠中呈现出降低肝糖生成的趋势^[1]。
Carmegliptin (10 mg/kg；口服；单次给药) (hydrochloride) 可使 db/db 小鼠的空腹血糖出现显著降低，并使口服葡萄糖耐量试验的 AUC_0-t 降低 30%^[1]。
Carmegliptin (3 mg/kg；口服；单次给药) (hydrochloride) 可在非糖尿病食蟹猴中产生持续的血浆 DPP-IV 抑制作用，给药后 24 小时和 48 小时分别残留 40% 和 60% 的基线活性^[1]。

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

450.37

C₂₀H₃₀Cl₂FN₃O₃

813452-14-1

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]