Discovery of Novel MDH2 Inhibitor

Lingyu Wu, Ru Zeng, Shuman Huang, Jiale Wu, Yu Ai, Zhifan Mao, Zhiguo Yang, Dan Liu, Yi-You Huang, Jian Li, Wenwen Liu, Zelan Hu, Baoli Li

Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China.Key Laboratory of Tropical Biological Resources of Ministry of Education and Hainan Engineering Research Center for Drug Screening and Evaluation, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, China. · pubmed

Paper

Abstract

Aging is a major public health challenge that urgently requires effective pharmacological interventions. We previously identified mitochondrial malate dehydrogenase 2 (MDH2) as a regulator of aging and discovered that the approved drug glibenclamide (Gli) can inhibit MDH2 and delay aging, but is limited by weak potency and hypoglycemia. Herein, we employed a rational secondary development strategy to optimize Gli and discovered compound

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Research summary

The paper claims to have discovered a novel inhibitor of MDH2 that could potentially delay aging. The research focuses on a specific target related to aging, aiming to develop pharmacological interventions that address the underlying mechanisms of aging rather than merely treating age-related symptoms.

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