(Rac)-Sitagliptin  (Synonyms: (Rac)-MK-0431)

(Rac)-Sitagliptin is an isoform of Sitagliptin (HY-13749), which is a potent and orally active inhibitor of DPP4 with an IC₅₀ of 19 nM in Caco-2 cell extracts^[1].

Sitagliptin 磷酸盐对 DPP-4 具有有效的抑制作用，Caco-2 细胞提取物中的 IC₅₀ 为 19 nM^[1]。
Sitagliptin 通过涉及 cAMP/PKA/Rac1 激活的途径减少分离的脾 CD4 T 细胞的体外迁移^[2]。
Staglitin 发挥一种新颖的直接作用，通过不依赖 DPP-4、依赖于蛋白激酶 A 和 MEK-ERK1/2 的途径刺激肠道 L 细胞分泌 GLP-1。它可以降低自身免疫对移植物存活的影响^[3]。

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

体内，在自由喂养的 Han-Wistar 中，磷酸 Sitagliptin 抑制大鼠血浆 DPP-4 活性的 ED₅₀ 值为 2.3 mg/kg (给药后 7 小时) 和 30 mg/kg (给药后 24 小时)^[1]。链脲佐菌素诱导的 1 型糖尿病小鼠模型中，血浆的 DPP-4 水平升高，而在服用磷酸 Sitagliptin 的小鼠中，DPP-4 水平可得到显着抑制。这是通过对高血糖调节的积极作用来实现的，可能是通过延长胰岛移植物的存活^[4]。大鼠中磷酸 Sitagliptin 的血浆清除率和分布容积（40-48 mL/min/kg，7-9 L/kg）高于狗（9 mL/min/kg，3 L/kg）；其半衰期在大鼠中较短，为 2 小时，而在狗中为 4 小时^[5]。

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

407.31

C₁₆H₁₅F₆N₅O

823817-56-7

Room temperature in continental US; may vary elsewhere.

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

• [1]. Beconi, M.G., et al. Disposition of the dipeptidyl peptidase 4 inhibitor sitagliptin in rats and dogs. Drug Metab Dispos, 2007. 35(4): p. 525-32.  [Content Brief]

  [2]. Thomas, L., et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther. 2008 Apr;325(1):175-82.  [Content Brief]

  [3]. Kim, S.J., et al., Dipeptidyl peptidase IV inhibition with MK0431 improves islet graft survival in diabetic NOD mice partially via T-cell modulation. Diabetes, 2009. 58(3): p. 641-51.  [Content Brief]

  [4]. Sangle, G.V., et al., Novel biological action of the dipeptidylpeptidase-IV inhibitor, sitagliptin, as a GLP-1 secretagogue. Endocrinology, 2012. 153(2): p. 564-73.  [Content Brief]

  [5]. Kim, S.J., et al., Inhibition of dipeptidyl peptidase IV with sitagliptin (MK0431) prolongs islet graft survival in streptozotocin-induced diabetic mice. Diabetes, 2008. 57(5): p. 1331-9.  [Content Brief]