CP-673451 (C007B-101522)

InformationCP-673451 is a selective inhibitor ofPDGFRα/βwithIC50of 10 nM/1 nM in cell-free assays, exhibits >450-fold selectivity over other angiogenic receptors, has antiangiogenic and antitumor activity.In vitroCP 673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM, exhibits >450-fold selectivity over other angiogenic receptors. In glioblastoma tumors, CP-673451 (33 mg/kg) provides >50% inhibition of PDGFR-β receptor for 4 hours corresponding to an EC50 of 120 ng/mL in plasma at Cmax. In a sponge angiogenesis model, CP-673451 inhibits 70% of PDGF-BB-stimulated angiogenesis at a dose of 3 mg/kg (q.d. ×5, p.o., corresponding to 5.5 ng/mL at Cmax). CP-673451 decreases cell proliferation rate through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. In both RD and RUCH2 cultures, CP-673451 impairs rhabdosphere-forming capacity and cell differentiation, causes increased senescence.In vivoCP 673451 (once-daily p.o. ?0 days dosing routinely) inhibits tumor growth (ED50 < 33 mg/kg) in a number of human tumor xenografts grown s.c. in athymic mice, including H460 human lung carcinoma, Colo205 and LS174T human colon carcinomas, and U87MG human glioblastoma multiforme. In RUCH2 xenograft-bearing mice, CP 673451 reduces tumor growth and stromal cell infiltration.Cell Datacell lines：Concentrations：~3000 nMIncubation Time：18 minPowder Purity:≥99%. Specification: 10mM in DMSO Molecular Formula: C24H27N5O2 Molecular Weight: 417.5