Cell-active dual specificity phosphatase inhibitors identified by high-content screening
Cell-active dual specificity phosphatase inhibitors identified by high-content screening
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DOI：
10.1016/s1074-5521(03)00170-4
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发表时间：
2003-08-01
影响因子：
--
通讯作者：
Lazo, JS
中科院分区：
文献类型：
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作者：
Vogt, A;Cooley, KA;Lazo, JS
细胞外信号调节激酶（Erk）的磷酸化受双特异性磷酸酶（DSPases）的严格控制，但很少有Erk去磷酸化的抑制剂被鉴定出来。使用高含量，基于荧光的细胞测定和国家癌症研究所的1990年代理多样性集，我们确定了10种化合物（0.5%），显着增加磷酸化ERK细胞核的差异在完整的细胞。10种阳性化合物中有3种在体外抑制丝裂原活化蛋白激酶磷酸酶-3（MKP 3/PYST-1），而不影响VHR或PTP 1B磷酸酶。最有效的MKP-3抑制剂的IC 50为
Phosphorylation of extracellular signal-regulated kinase (Erk) is tightly controlled by dual specificity phosphatases (DSPases), but few inhibitors of Erk dephosphorylation have been identified. Using a high-content, fluorescence-based cellular assay and the National Cancer Institute's 1990 agent Diversity Set, we identified ten compounds (0.5%) that significantly increased phospho-Erk cytonuclear differences in intact cells. Three of the ten positive compounds inhibited the mitogen-activated protein kinase phosphatase-3 (MKP3/PYST-1) in vitro without affecting VHR or PTP1B phosphatases. The most potent inhibitor of MKP-3 had an IC50 of