Inhibition of FGF-1 receptor tyrosine kinase activity by PD 161570, a new protein-tyrosine kinase inhibitor

被引：20

作者：

Batley, BL

Doherty, AM

Hamby, JM

Lu, GH

Keller, P

Dahring, TK

Hwang, O

Crickard, K

Panek, RL

机构：

[1] Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Dept Therapeut, Ann Arbor, MI 48105 USA

[2] Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Dept Chem, Ann Arbor, MI 48105 USA

[3] SUNY Coll Buffalo, Dept Obstet & Gynecol, Buffalo, NY 14222 USA

来源：

LIFE SCIENCES | 1997年 / 62卷 / 02期

关键词：

FGF-1 receptor tyrosine kinase; PD; 161570; tyrosine phosphorylation; angiogenesis;

D O I：

10.1016/S0024-3205(97)01060-6

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：143 / 150

页数：8

共 35 条

[31] GROWTH-FACTORS AND ANGIOGENESIS [J].