INHIBITION OF FGF-1 RECEPTOR TYROSINE KINASE-ACTIVITY BY PD-161570, ANEW PROTEIN-TYROSINE KINASE INHIBITOR

Through direct synthetic efforts we discovered a small molecule which is a 40 nanomolar inhibitor of the human FGF-1 receptor tyrosine kinas e. mino-butylamino)-pyrido[2,3-d]pyrimidin-7-yl]-urea (PD 161570) had about 5- and 100-fold greater selectivity toward the FGF-I receptor (I C50 = 40 nM) compared with the PDGF beta receptor (IC50 = 262 nM) or E GF receptor (IC50 = 3.7 mu M) tyrosine kinases, respectively. In addit ion, PD 161570 suppressed constitutive phosphorylation of the FGF-I re ceptor in both human ovarian carcinoma cells (A121(p)) and Sf9 insect cells overexpressing the human FGF-1 receptor and blocked the growth o f A121(p) cells in culture. The results demonstrate a novel synthetic inhibitor with nanomolar potency and specificity towards the FGF-T rec eptor tyrosine kinase.