小分子葡萄糖激酶激活剂研究进展

Reaserch Advances of Small Molecular Activators of Glucokinase

葡萄糖激酶是四种己糖激酶之一,在肝脏中促进肝糖原的合成减少肝糖输出,胰岛β细胞中调控糖促胰岛素的分泌,在维持体内血糖起重要作用。葡萄糖激酶是治疗Ⅱ型糖尿病新靶点,小分子葡萄激酶激活剂通过激活葡萄糖激酶,提高葡萄糖激酶与葡萄糖的亲和力,增大葡萄糖激酶最大酶促反应速率,达到降血糖的作用。目前已有20多个候选药物进入临床试验,最快的已进入Ⅲ期临床,主要有完全激活剂、肝选择性激活剂两类。

Glucokinase is one of four members of the hexokinase. In the liver,it promotes the synthesis of hepatic glycogen and reduces hepatic glucose output. In pancreatic β-cell,it regulates the secretion of insulin. It＇ s lowering blood glucose in liver and pancreas play an important role in glucosehomeostasis. Glucokinase is a new target for the therapy of type 2 diabetes. Small molecular activators of glucokinase can increase the affinity of glucokinase with glucose and the maximal enzymatic reaction rate of glucokinase by activated glucokinase. As so far,there are more than20 candidate drugs into clinical trials,the fastest has entered Phase Ⅲ clinical. GKA are divided into complete activators and liver selective activators.