Inhibition of FGF-1 receptor tyrosine kinase activity by PD 161570, a new protein-tyrosine kinase inhibitor
Inhibition of FGF-1 receptor tyrosine kinase activity by PD 161570, a new protein-tyrosine kinase inhibitor
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DOI：
10.1016/s0024-3205(97)01060-6
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发表时间：
1997-12-05
期刊：
影响因子：
6.1
通讯作者：
Panek, RL
中科院分区：
文献类型：
--
作者：
Batley, BL;Doherty, AM;Panek, RL
Through direct synthetic efforts we discovered a small molecule which is a 40 nanomolar inhibitor of the human FGF-1 receptor tyrosine kinase. 1-Tert-butyl-3-[6-(2,6-dichloro-phenyl)-2-(4-diethylamino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea (PD 161570) had about 5- and 100-fold greater selectivity toward the FGF-I receptor (IC50 = 40 nM) compared with the PDGF beta receptor (IC50 = 262 nM) or EGF receptor (IC50 = 3.7 mu M) tyrosine kinases, respectively. In addition, PD 161570 suppressed constitutive phosphorylation of the FGF-I receptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth of A121(p) cells in culture. The results demonstrate a novel synthetic inhibitor with nanomolar potency and specificity towards the FGF-T receptor tyrosine kinase.
