Table 1.

Effects of KRN951 on the ligand-stimulated phosphorylation of receptor tyrosine kinases

RTKCellIC50 (nmol/L)95% Confidence interval (nmol/L)Fold selectivity vs VEGFR-2 *
VEGFR-2HUVEC0.160.13-0.201
VEGFR-1NIH3T3-Flt-1 0.210.16-0.301.3
VEGFR-3HUVEC0.240.16-0.341.5
c-KitKU812F1.631.13-2.3510
PDGFR-βNHDF1.721.39-2.1311
Flt3Eol-1422342-5222,640
FGFR1NHDF299214-4171,870
c-MetA4311,360730-2,5408,500
EGFRA431ND
IGF-1RHT29ND
  • NOTE: IC50 values and their 95% confidence intervals were calculated by nonlinear regression analysis of the percentage inhibitions (n = 4).

    Abbreviations: NHDF, normal human dermal fibroblast; RTK, receptor tyrosine kinase; ND, not determined.

  • * Ratio for the IC50 was obtained with a given RTK compared with that achieved against VEGFR-2.

  • Flt-1–transfected NIH3T3.

  • IC50 values could not be determined because KRN951 was apparently insoluble in the medium at the concentrations tested.