PD173074 inhibits FGFR3 autophosphorylation and malignant transformation by activated FGFR3. (A) Immunoblot analyses of WT FGFR3-expressing NIH 3T3 cells after incubation with PD173074, with (+) or without (-) aFGF/heparin stimulation. Anti-FGFR3 (αFGFR3) immunoprecipitates (IP) immunoblotted (IB) with anti-phosphotyrosine (4G10; top) and anti-FGFR3 (bottom). (B) NIH 3T3 cells transfected with WT FGFR3, constitutively active Y373C FGFR3, or Ras V12 were cultured in the absence (-) or presence of 25 nM PD173074. Fourteen days after transfection cellular foci were stained. (C) The 5 × 105 NIH 3T3 cells transfected with Y373C FGFR3 (right flank) or Ras V12 (left flank) were injected subcutaneously into nude mice. Mice were treated with either placebo (left) or 20 mg/kg PD173074 (right) for 9 consecutive days. Representative mice are shown 19 days after tumor injection.
