Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia.
Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia.
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DOI：
10.1021/ml200239k
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发表时间：
2012-02-09
影响因子：
4.2
通讯作者：
Wang, Xiaodong
中科院分区：
文献类型：
--
作者：
Liu, Jing;Yang, Chao;Simpson, Catherine;DeRyckere, Deborah;Van Deusen, Amy;Miley, Michael J.;Kireev, Dmitri;Norris-Drouin, Jacqueline;Sather, Susan;Hunter, Debra;Korboukh, Victoria K.;Patel, Hari S.;Janzen, William P.;Machius, Mischa;Johnson, Gary L.;Earp, H. Shelton;Graham, Douglas K.;Frye, Stephen V.;Wang, Xiaodong
Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design.
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影响因子：
3
作者：
Huang, Xudong;Finerty, Patrick, Jr.;Walker, John R.;Butler-Cole, Christine;Vedadi, Masoud;Schapira, Matthieu;Parker, Sirlester A.;Turk, Benjamin E.;Thompson, Debra A.;Dhe-Paganon, Sirano
通讯作者：
Dhe-Paganon, Sirano
影响因子：
--
作者：
Pommereau, A;Pap, E;Kannt, A
通讯作者：
Kannt, A
影响因子：
2.7
作者：
Schenone, S;Bruno, O;Botta, M
通讯作者：
Botta, M
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.2
作者：
Klein, Michael;Diner, Peter;Grotli, Morten
通讯作者：
Grotli, Morten