Table 1.

Effect of PF-04217903 on c-Met–dependent cellular phenotypes in vitro

PF-04217903 concentration
Assayc-Met statusIC50,a nmol/L
Tumor cell phenotypes
 Proliferation (MTT assay) of GTL-16 gastric carcinoma cells (mean IC50)Gene amplification11.5
 Proliferation (MTT assay) of NCI-H1993 lung carcinoma cells (mean IC50)Gene amplification30
 Proliferation (MTT assay) of a panel of tumor cell linesb (mean IC50)Overexpression/autocrine>10,000
 Apoptosis (ssDNA assay) of GTL-16 gastric carcinoma cells (mean IC50)Gene amplification31
 HGF-stimulated HT29 cell (Boyden Chamber Matrigel invasion; mean IC50)Overexpression7
 HGF-stimulated NCI-H441 cell migration (Acea System; IC50)Overexpression11
 HGF-stimulated NCI-H441 cell invasion (Acea System; IC50)Overexpression12.5
Endothelial cell phenotypes
 HGF-stimulated HUVEC survival (MTT assay; mean IC50)Normal12.3
 HGF-stimulated HUVEC Matrigel invasion (Acea System; IC50)Normal27
 Apoptosis (ssDNA assay) of HUVEC cells (IC50)Normal7.3

Abbreviation: ss, single-stranded.

  • aIC50 values were generated by curve fitting using a 4-parameter analysis.

  • bThe panel of tumor cell lines includes Colo205, HT29, SW620, HCT116, DLD1, MDA-MB-231, MDA-MB-468, HCC1143, A549, U87MG, PC3, and others.