醛糖还原酶
多元醇途径
限制
药理学
酶
选择性
醛还原酶
毒性
医学
化学
生物化学
醛糖还原酶抑制剂
催化作用
内科学
机械工程
工程类
作者
Manoj Kumar,Shalki Choudhary,Pankaj Kumar Singh,Om Silakari
出处
期刊:Future Medicinal Chemistry
[Newlands Press Ltd]
日期:2020-07-01
卷期号:12 (14): 1327-1358
被引量:15
标识
DOI:10.4155/fmc-2020-0032
摘要
Aldose Reductase 2 (ALR2), the rate-limiting enzyme of the polyol pathway, plays an important role in detoxification of some toxic aldehydes. Under hyperglycemia, this enzyme overactivates and causes diabetic complications (DC). Therefore, ALR2 inhibition has been established as a potential approach to manage these complications. Several ALR2 inhibitors have been reported, but none of them could reach US FDA approval. One of the main reasons is their poor selectivity over ALR1, which leads to the toxicity. The current review underlines the molecular connectivity of ALR2 with DC and comparative analysis of the catalytic domains of ALR2 and ALR1, to better understand the selectivity issues. This report also discusses the key features required for ALR2 inhibition and to limit toxicity due to off-target activity.
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