Diverse heterocyclic scaffolds as allosteric inhibitors of AKT

…, C Crafter, BR Davies, P Dudley, G Fairley…

Index: Kettle, Jason G.; Brown, Simon; Crafter, Claire; Davies, Barry R.; Dudley, Phillippa; Fairley, Gary; Faulder, Paul; Fillery, Shaun; Greenwood, Hannah; Hawkins, Janet; James, Michael; Johnson, Keith; Lane, Clare D.; Pass, Martin; Pink, Jennifer H.; Plant, Helen; Cosulich, Sabina C. Journal of Medicinal Chemistry, 2012 , vol. 55, # 3 p. 1261 - 1273

Full Text: HTML

Citation Number: 39

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 ...