ZD-4190是VEGF RTK抑制剂，对KDR和Flt-1的IC50值分别为29 ± 4 nM和708 ± 63 nM。 Information ZD-4190 is a submicromolar inhibitor ofVEGF RTKactivity in vitro with IC50 values of 29 ± 4 nM and 708 ± 63 nM for KDR and Flt-1, respectively. Targets KDR ; Flt-1 In vitro ZD4190 is a submicromolar inhibitor of VEGF RTK activity in vitro with greatest effect against KDR. Selectivity versus FGFR1 tyrosine kinase activity is demonstrated, with at least a 30-fold difference in the IC50 required to inhibit HUVEC proliferation stimulated by VEGF or bFGF, respectively. No effects on basal HUVEC growth are observed, even at the maximum ZD4190 concentration examined in these assays (10 μM). In vivo Chronic once-daily oral dosing of ZD4190 to young rats produces a dose-dependent increase in the femoral epiphyseal growth plate area. Once-daily oral dosing of ZD4190 to mice bearing established (∼0.5 cm 3 ) human tumor xenografts (breast, lung, prostate, and ovarian) elicits significant antitumor activity and at doses that would not be expected to have any direct antiproliferative effect on tumor cells. In a PC-3 xenograft model, 10 weeks of ZD4190 dosing prolongs tumor cytostasis and upon withdrawal of therapy, tumor growth resumed after a short delay.