2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2006 Mar 15;16(6):1679-85. doi: 10.1016/j.bmcl.2005.12.017.
Qun Li 1,  Tongmei Li,  Gui-Dong Zhu,  Jianchun Gong,  Akiyo Claibone,  Chris Dalton,  Yan Luo,  Eric F Johnson,  Yan Shi,  Xuesong Liu,  Vered Klinghofer,  Joy L Bauch,  Kennan C Marsh,  Jennifer J Bouska,  Shannon Arries,  Ron De Jong,  Tilman Oltersdorf,  Vincent S Stoll,  Clarissa G Jakob,  Saul H Rosenberg,  Vincent L Giranda
Affiliations

Affiliation

  • 1 Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. [email protected]
PMID: 16403626 DOI: 10.1016/j.bmcl.2005.12.017
Abstract

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 IC(50) 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.

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  • HY-123390
    T315I Mutant Bcr-Abl Inhibitor