Substituted oxindol-3-ylidenes as AMP-activated protein kinase (AMPK) inhibitors.

ABSTRACT: AMP-activated protein kinase (AMPK) is a central metabolic regulator that promotes cancer growth and survival under hypoxia and plays a role in the maintenance of cancer stem cells. A major challenge to interrogating the potential of targeting AMPK in cancer is the lack of potent and selective small molecule inhibitors. Compound C has been widely used as an AMPK inhibitor, but it lacks potency and has a poor selectivity profile. The multi-kinase inhibitor, sunitinib, has demonstrated potent nanomolar inhibition of AMPK activity and has scope for modification. Here, we have designed and synthesized several series of oxindoles to determine the structural requirements for AMPK inhibition and to improve selectivity. We identified two potent, novel oxindole-based AMPK inhibitors that were desig

SUBMITTER: Matheson CJ 

PROVIDER: S-EPMC7409528 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature