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糖原合酶激酶-3:糖尿病的一个潜在靶点。

Glycogen synthase kinase-3: A potential target for diabetes.

机构信息

Department of Pharmaceutical Chemistry and Quality Assurance, L. M. College of Pharmacy, Ahmedabad, Gujarat 380009, India.

Department of Pharmaceutical Chemistry and Quality Assurance, L. M. College of Pharmacy, Ahmedabad, Gujarat 380009, India.

出版信息

Bioorg Med Chem. 2023 Sep 7;92:117406. doi: 10.1016/j.bmc.2023.117406. Epub 2023 Jul 6.

Abstract

Elevated circulating glucose level due to β-cell dysfunction has been a key marker of Type-II diabetes. Glycogen synthase kinase-3 (GSK-3) has been recognized as an enzyme involved in the control of glycogen metabolism. Consequently, inhibitors of GSK-3 have been explored for anti-diabetic effects in vitro and in animal models. Further, the mechanisms governing the regulation of this enzyme have been elucidated by means of a combination of structural and cellular biological investigations. This review article examines the structural analysis of GSK-3 as well as molecular modeling reports from numerous researchers in the context of the design and development of GSK-3 inhibitors. This article centers on the signaling pathway of GSK-3 relevant to its potential as a target for diabetes and discusses advancements till date on different molecular modification approaches used by researchers in the development of novel GSK-3 inhibitors as potential therapeutics for the treatment of Type II diabetes.

摘要

由于β细胞功能障碍导致的循环葡萄糖水平升高一直是 II 型糖尿病的一个重要标志物。糖原合酶激酶-3(GSK-3)已被认为是参与控制糖原代谢的一种酶。因此,GSK-3 的抑制剂已在体外和动物模型中被探索用于抗糖尿病作用。此外,通过结构和细胞生物学研究的结合,已经阐明了调节该酶的机制。本文综述了 GSK-3 的结构分析以及许多研究人员的分子建模报告,内容涉及 GSK-3 抑制剂的设计和开发。本文围绕与 GSK-3 作为糖尿病治疗靶点的潜在性相关的信号通路展开讨论,并讨论了迄今为止研究人员在开发新型 GSK-3 抑制剂作为 II 型糖尿病潜在治疗药物方面的不同分子修饰方法的进展。

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