Diverse Heterocyclic Scaffolds as Allosteric Inhibitors of AKT
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- 作者：Jason G. Kettle ; 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
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：February 9, 2012
- 年：2012
- 卷：55
- 期：3
- 页码：1261-1273
- 全文大小：523K
- 年卷期：v.55,no.3(February 9, 2012)
- ISSN：1520-4804
文摘
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.