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Dorzagliatin

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Chemical Structure| 1191995-00-2 同义名 : HMS5552;RO-5305552;Sinogliatin
CAS号 : 1191995-00-2
货号 : A642740
分子式 : C22H27ClN4O5
纯度 : 99%+
分子量 : 462.927
MDL号 : MFCD22376579
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(259.22 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Glucokinase (GK) is a key regulatory enzyme in whole-body glucose homeostasis. Dorzagliatin is a novel GK activator that has been shown to decrease blood glucose levels and improves GK activity and insulin resistance. Two hours after a single intragastric administration of 10 mg/kg or 30 mg/kg dorzagliatin decreased glucose levels in diabetic rats by ~25% and 31%, respectively, compared with the levels measured before dorzagliatin treatment. After 27 days of treatment, a significant reduction in fasting plasma glucose levels was observed in dorzagliatin-treated diabetic rats compared to the vehicle-treated group. Also, rats administered with 10 mg/kg or 30 mg/kg dorzagliatin showed a reduction in glucose levels (~18% and 23%, respectively) measured 2h after HMS5552 administration compared with the levels detected before dorzagliatin administration. Treatment of diabetic rats with 10 mg/kg and 30 mg/kg dorzagliatin also significantly decreased the levels of fasting insulin compared with the diabetic group. Rats treated with dorzagliatin (10 mg/kg and 30 mg/kg) for one months showed significantly decreased Km value of GK (5.9 ± 0.43mmol/L and 5.6 ± 0.27mmol/L, respectively) compared to the diabetic group (9.9 ± 0.55mmol/L). After dorzagliatin treatment, the number of GK- and insulin-immunopositive cells was also significantly increased in diabetic rats. The protein and mRNA expressions of GK in dorzagliatin-treated rats were significantly higher than those observed in the diabetic group.[3]
作用机制 Dorzagliatin is a fourth-generation GK activator with a structurally novel amino-acid-based chemical scaffold, which improves GK activity in a rat model of T2DM induced by a high-fat diet and streptozotocin.[3]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.16mL

0.43mL

0.22mL

10.80mL

2.16mL

1.08mL

21.60mL

4.32mL

2.16mL
参考文献

[1]Wang P, Liu H, et al. Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus. J Diabetes Res. 2017;2017:5812607.

[2]Xu H, Sheng L, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study. Drug Des Devel Ther. 2016 May 9;10:1619-26.

[3]Wang P, Liu H, Chen L, Duan Y, Chen Q, Xi S. Effects of a Novel Glucokinase Activator, HMS5552, on Glucose Metabolism in a Rat Model of Type 2 Diabetes Mellitus. J Diabetes Res. 2017;2017:5812607. doi:10.1155/2017/5812607