Diverse heterocyclic scaffolds as allosteric inhibitors of AKT

  • J Med Chem. 2012 Feb 9;55(3):1261-73. doi: 10.1021/jm201394e.
Jason G Kettle  1 ,  Simon Brown ,  Claire Crafter ,  Barry R Davies ,  Phillippa Dudley ,  Gary Fairley ,  Paul Faulder ,  Shaun Fillery ,  Hannah Greenwood ,  Janet Hawkins ,  Michael James ,  Keith Johnson ,  Clare D Lane ,  Martin Pass ,  Jennifer H Pink ,  Helen Plant ,  Sabina C Cosulich
Affiliations
  • 1. Oncology iMED, AstraZeneca, Alderley Park, Macclesfield, SK10 4TG, United Kingdom. [email protected]
PMID: 22248236 DOI: 10.1021/jm201394e
Abstract

Wide-ranging exploration of potential replacements for a quinoline-based inhibitor of activation of Akt kinase led to number of alternative, novel scaffolds with potentially improved potency and physicochemical properties. Examples showed predictable DMPK properties, and one such compound demonstrated pharmacodynamic knockdown of phosphorylation of Akt and downstream biomarkers in vivo and inhibition of tumor growth in a breast Cancer xenograft model.

Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-18296
    AKT-IN-1
    98.41%, Akt Inhibitor
    target: Akt
    Research Areas: Cancer