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

  • Bioorg Med Chem Lett. 2014 Oct 1;24(19):4650-4653. doi: 10.1016/j.bmcl.2014.08.040.
Young B Kim  1 ,  Chang Won Kang  1 ,  Sujeewa Ranatunga  1 ,  Hua Yang  1 ,  Said M Sebti  1 ,  Juan R Del Valle  1
Affiliations
  • 1. Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
PMID: 25205195 DOI: 10.1016/j.bmcl.2014.08.040
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.

Keywords
Dipeptide surrogate; Kinase inhibitor; Peptide mimic; β-Strand mimic.
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