Cediranib

288383-20-0

C25H27FN4O3

DMSO : >= 49 mg/mL (108.77 mM); H2O : < 0.1 mg/mL (insoluble)

Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK; Autophagy

Cediranib (AZD2171) is a highly potent, orally available VEGFR tyrosine kinase inhibitor with IC₅₀s of <1, <3, 5, 5, 36, 2 nM for Flt1, KDR, Flt4, PDGFRalpha, PDGFRbeta, c-Kit, respectively. IC50 & Target: IC50: <1 nM (Flt1), <3 nM (KDR), 5 nM (Flt4), 5 nM (PDGFRalpha), 36 nM (PDGFRbeta), 2 nM (c-Kit)^[1] In Vitro: In human umbilical vein endothelial cells, Cediranib inhibits VEGF-stimulated proliferation and KDR phosphorylation with IC₅₀ values of 0.4 and 0.5 nM, respectively. In a fibroblast/endothelial cell coculture model of vessel sprouting, Cediranib also reduces vessel area, length, and branching at subnanomolar concentrations^[1]. In Vivo: Once-daily oral administration of Cediranib ablates experimental (VEGF-induced) angiogenesis and inhibits endochondral ossification in bone or corpora luteal development in ovary; physiologic processes that are highly dependent upon neovascularization. The growth of established human tumor xenografts (colon, lung, prostate, breast, and ovary) in athymic mice is inhibited dose-dependently by Cediranib, with chronic administration of 1.5 mg per kg per day producing statistically significant inhibition in all models. A histologic analysis of Calu-6 lung tumors treated with Cediranib reveals a reduction in microvessel density within 52 hours that becomes progressively greater with the duration of treatment. These changes are indicative of vascular regression within tumors^[1].