PD173074 is an effective FGFR1 inhibitor (IC50: 25 nM) and also inhibits VEGFR2 (IC50: 100-200 nM) in cell-free assays. The selectivity is higher ~1000-fold for FGFR1 than PDGFR and c-Src.

FGFR1:25 nM, VEGFR2:100 nM-200 nM

在KMS11异种移植瘤模型中,PD173074抑制FGFR3造成的肿瘤生长延缓,提高小鼠存活率. 在H-510异种移植体中,PD173074与顺铂阻断肿瘤生长的作用相似,与对照组相比中位生存期增加.在H-69异种移植体中,PD173074对50％小鼠的诱导作用大于6个月.PD173074（1/2 mg/kg/day）剂量依赖性地有效阻止由成纤维生长因子或血管内皮生长因子诱导的小鼠血管生成,且无明显毒性.在裸鼠体内,PD173074对NIH 3T3细胞（成纤维细胞生长因子受体3突变体转染）生长有抑制作用.

PD173074剂量依赖性地抑制VEGFR2（IC50：100-200 nM）和FGFR1（IC50：1-5 nM）的自身磷酸化。 PD173074剂量依赖性抑制FGF-2促进的颗粒神经元存活（IC50：12 nM）,比SU 5402活性高1,000倍以上。 PD173074对FGF-2-介导的少突胶质细胞谱系细胞的细胞增殖、分化及MAPK激活具有特异性的抑制作用。PD173074是ATP竞争性的FGFR1抑制剂（Ki：40 nM）。PD173074还剂量依赖性地有效抑制FGFR3的自磷酸化（IC50：5 nM）。在多发性骨髓瘤细胞系中,PD173074对野生型及FGFR3突变型有活性。PD173074使表达FGFR3的KMS11细胞和KMS18细胞的活力显著下降（IC50<20 nM）。

In vitro kinase inhibition assays: Assays using the full-length FGFR-1 kinase are performed in a total volume of 100 μL containing 25 mM HEPES buffer (pH 7.4), 150 mM NaCl, 10 mM MnCl2, 0.2 mM sodium orthovanadate, 750 μg/mL concentration of a random copolymer of glutamic acid and tyrosine (4:1), various concentrations of PD173074 and 60 to 75 ng of enzyme. The reaction is initiated by the addition of [γ-32P]ATP (5 μM ATP containing 0.4 μCi of [γ-32P]ATP per incubation), and samples are incubated at 25°C for 10 minutes. The reaction is terminated by the addition of 30% trichloroacetic acid and the precipitation of material onto glass-fiber filter mats. Filters are washed three times with 15% trichloroacetic acid, and the incorporation of [32P] into the glutamate tyrosine polymer substrate is determined by counting the radioactivity retained on the filters in a Wallac 1250 betaplate reader. Nonspecific activity is defined as radioactivity retained on the filters following incubation of samples without enzyme. Specific activity is determined as total activity (enzyme plus buffer) minus nonspecific activity. The concentration of PD173074 that inhibits FGFR-1 enzymatic activity by 50% (IC50) is determined graphically.

Cells are incubated with increasing concentrations of PD173074 in the presence of aFGF/heparin for 48 hours. The percentage of viable cells is determined by MTT.(Only for Reference)