PD 173074 is a potent ATP-competitive inhibitor of fibroblast growth factor receptor 1 and 3. PD173074 is also an effective inhibitor of FGFR2, FGFR4, and VEGFR2. Compared to FGFR1, PD173074 weakly inhibits the activities of Src, InsR, EGFR, PDGFR, MEK, and PKC with 1000-fold or greater IC50 values. PD173074 inhibits autophosphorylation of FGFR1 and VEGFR2 in a dose-dependent manner with IC50 of 1-5 nM and 100-200 nM, respectively. PD173074 specifically inhibits FGF-2-mediated effects on proliferation, differentiation, and MAPK activation in oligodendrocyte (OL) lineage cells. PD173074 treatment potently reduces the viability of FGFR3-expressing KMS11 and KMS18 cells. Inhibition of aFGF-stimulated MM cell growth by PD173074 is highly correlated with the expression of FGFR3. PD173074 treatment completely abolishes NIH 3T3 transformation mediated by Y373C FGFR3 but not by Ras V12, demonstrating that PD173074 specifically targets FGFR3-mediated cell transformation and lacks nonspecific cytotoxic effect. Administration of PD173074 at 1 mg/kg/day or 2 mg/kg/day in mice can effectively block angiogenesis induced by either FGF or VEGF in a dose-dependent manner with no apparent toxicity. PD173074 inhibits in vivo growth of mutant FGFR3-transfected NIH 3T3 cells in nude mice. Inhibition of FGFR3 by PD173074 delays tumor growth and increases survival of mice in a KMS11 xenograft myeloma model. In the H-510 xenograft, oral administration of PD173074 blocks tumor growth similar to that seen with single-agent cisplatin administration, increasing median survival compared with control sham-treated animals. In H-69 xenografts, PD173074 induces complete responses lasting >6 months in 50% of mice. These effects are correlated with increased apoptosis in excised tumors, but not a consequence of disrupted tumor vasculature. PD173074 seems to be discontinued in the preclinical development stage, and no clinical data are available currently.