882169-89-3Relevant academic research and scientific papers
Discovery of trans-3,4′-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: Synthesis and biological evaluation
Li, Qun,Li, Tongmei,Zhu, Gui-Dong,Gong, Jianchun,Claibone, Akiyo,Dalton, Chris,Luo, Yan,Johnson, Eric F.,Shi, Yan,Liu, Xuesong,Klinghofer, Vered,Bauch, Joy L.,Marsh, Kennan C.,Bouska, Jennifer J.,Arries, Shannon,De Jong, Ron,Oltersdorf, Tilman,Stoll, Vincent S.,Jakob, Clarissa G.,Rosenberg, Saul H.,Giranda, Vincent L.
, p. 1679 - 1685 (2007/10/03)
A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3,4′-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC50 values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the AGC and CMGC families. The cellular activities including inhibition of cell growth and phosphorylation of downstream target GSK3 are also described. The X-ray structure of compound 2q complexed with PKA in the ATP binding site was determined.
Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase
Thomas, Sheela A.,Li, Tongmei,Woods, Keith W.,Song, Xiaohong,Packard, Garrick,Fischer, John P.,Diebold, Robert B.,Liu, Xuesong,Shi, Yan,Klinghofer, Vered,Johnson, Eric F.,Bouska, Jennifer J.,Olson, Amanda,Guan, Ran,Magnone, Shayna R.,Marsh, Kennan,Luo, Yan,Rosenberg, Saul H.,Giranda, Vincent L.,Li, Qun
, p. 3740 - 3744 (2007/10/03)
Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure-activity relationship studies, and pharmacokinetic data are presented in this paper.
