Document Report Card

ID: ALA1153413

Journal: J Med Chem

Title: Pyranonaphthoquinone lactones: a new class of AKT selective kinase inhibitors alkylate a regulatory loop cysteine.

Authors: Salaski EJ, Krishnamurthy G, Ding WD, Yu K, Insaf SS, Eid C, Shim J, Levin JI, Tabei K, Toral-Barza L, Zhang WG, McDonald LA, Honores E, Hanna C, Yamashita A, Johnson B, Li Z, Laakso L, Powell D, Mansour TS.

Abstract: The naturally occurring pyranonaphthoquinone (PNQ) antibiotic lactoquinomycin and related aglycones were found to be selective inhibitors of the serine-threonine kinase AKT. A set of synthetic PNQs were prepared and a minimum active feature set and preliminary SAR were determined. PNQ lactones inhibit the proliferation of human tumor cell lines containing constitutively activated AKT and show expected effects on cellular biomarkers. Biochemical data are presented supporting a proposed bioreductive alkylation mechanism of action.

CiteXplore: 19309081

DOI: 10.1021/jm900075g