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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Del Valle, Juan R.¹ 

[1] H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Dept, Tampa, FL 33612 USA

关键词: Kinase inhibitor;    Peptide mimic;    Dipeptide surrogate;    beta-Strand mimic;   

DOI  :  10.1016/j.bmcl.2014.08.040

来源: Elsevier

【 摘 要 】

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. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free