AMP 激活的蛋白激酶：药物研发的现状。

AMP-activated protein kinase: the current landscape for drug development.

机构信息

Centre for Metabolism, Obesity and Diabetes Research, Department of Medicine and Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.

Cellular Stress Group, Medical Research Council London Institute of Medical Sciences, Hammersmith Hospital, Imperial College, London, UK.

出版信息

Nat Rev Drug Discov. 2019 Jul;18(7):527-551. doi: 10.1038/s41573-019-0019-2.

DOI:10.1038/s41573-019-0019-2

PMID:30867601

Abstract

Since the discovery of AMP-activated protein kinase (AMPK) as a central regulator of energy homeostasis, many exciting insights into its structure, regulation and physiological roles have been revealed. While exercise, caloric restriction, metformin and many natural products increase AMPK activity and exert a multitude of health benefits, developing direct activators of AMPK to elicit beneficial effects has been challenging. However, in recent years, direct AMPK activators have been identified and tested in preclinical models, and a small number have entered clinical trials. Despite these advances, which disease(s) represent the best indications for therapeutic AMPK activation and the long-term safety of such approaches remain to be established.

摘要

自从 AMP 激活的蛋白激酶（AMPK）被发现为能量平衡的核心调节剂以来，人们对其结构、调节和生理作用有了许多令人兴奋的认识。虽然运动、热量限制、二甲双胍和许多天然产物可以增加 AMPK 的活性，并产生多种健康益处，但开发直接激活 AMPK 的药物以产生有益效果一直具有挑战性。然而，近年来，已经在临床前模型中鉴定和测试了直接 AMPK 激活剂，并且少数已经进入临床试验。尽管取得了这些进展，但仍需确定哪些疾病（或疾病组合）最适合治疗性 AMPK 激活，以及此类方法的长期安全性。