Aromatic Interactions with Phenylalanine 691 and Cysteine 828: A Concept for FMS-like Tyrosine Kinase-3 Inhibition. Application to the Discovery of a New Class of Potential Antileukemia Agents
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- 作者：Pascal Furet ; Guido Bold ; Thomas Meyer ; Johannes Roesel ; Vito Guagnano
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：July 27, 2006
- 年：2006
- 卷：49
- 期：15
- 页码：4451 - 4454
- 全文大小：193K
- 年卷期：v.49,no.15(July 27, 2006)
- ISSN：1520-4804
文摘
FLT3 kinase inhibitors are currently under investigation asa new treatment for acute myeloid leukemia. We report here a molecularconcept invoking interactions between an aromatic ring and the sidechains of Phe691 and Cys828, two residues of the ATP pocket, to obtainpotent and specific inhibitors of this kinase. The hypothesis has beenvalidated by the successful design of a new inhibitor prototype showingpromising antiproliferative activity in cellular assays.