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Imidazo[1,2-a]pyridine-based peptidomimetics as inhibitors of Akt.

ABSTRACT: We report the design, synthesis, and biological evaluation of imidazopyridine-based peptidomimetics based on the substrate consensus sequence of Akt, an AGC family serine/threonine kinase hyperactivated in over 50% of human tumors. Our ligand-based approach led to the identification of novel substrate mimetic inhibitors of Akt1 featuring an unnatural extended dipeptide surrogate. Compound 11 inhibits Akt isoforms in the sub-micromolar range and exhibits improved proteolytic stability relative to a parent pentapeptide.

SUBMITTER: Kim YB

PROVIDER: S-EPMC4176526 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Imidazo[1,2-a]pyridine-based peptidomimetics as inhibitors of Akt.

Kim Young B YB Kang Chang Won CW Ranatunga Sujeewa S Yang Hua H Sebti Said M SM Del Valle Juan R JR

Bioorganic & medicinal chemistry letters 20140828 19

We report the design, synthesis, and biological evaluation of imidazopyridine-based peptidomimetics based on the substrate consensus sequence of Akt, an AGC family serine/threonine kinase hyperactivated in over 50% of human tumors. Our ligand-based approach led to the identification of novel substrate mimetic inhibitors of Akt1 featuring an unnatural extended dipeptide surrogate. Compound 11 inhibits Akt isoforms in the sub-micromolar range and exhibits improved proteolytic stability relative to ...[more]

PMID: 25205195

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