CP-673451 is a potent inhibitor of PDGFR with IC50 value of 10nM and 1nM for PDGFR-α and PDGFR-β, respectively [1].
CP-673451 is an ATP-competitive inhibitor and is investigated to treat for cancer. It is highly selective against PDGFR-α and PDGFR-β over a variety of other kinases such as VEGFR-1, VEGFR-2, Lck, TIE-2 and EGFR. In PAE-β cells, CP-673451 inhibits PDGFR-β with IC50 value of 6.4nM. CP-673451 also inhibits c-kit with IC50 value of 1.1μM in H526 cells. In rat C6 glioblastoma xenograft models, a single oral dose of 50mg/kg CP-673451 reduces > 50% phosphorylation of PDGFR-β for 4 hours. In addition, CP-673451 is found to inhibit PDGF-BB-induced angiogenesis in a sponge angiogenesis model. Furthermore, CP-673451 inhibits the tumor growth in Colo205, LS174T, H460, and U87MG xenograft models. It also reduces the microvessel density of Colo205 xenografts [1].
References:
[1] Roberts W G, Whalen P M, Soderstrom E, et al. Antiangiogenic and antitumor activity of a selective PDGFR tyrosine kinase inhibitor, CP-673,451. Cancer research, 2005, 65(3): 957-966.