The rational design of a novel potent analogue of the 5'-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity.

ABSTRACT: We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5'-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK.

SUBMITTER: Machrouhi F 

PROVIDER: S-EPMC2957560 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature