Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis.

ABSTRACT: Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a K_D value of 4.728 × 10^-8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-08

SUBMITTER: Chen J 

PROVIDER: S-EPMC10232707 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature