C-4300 Cediranib, Free Base, >99%

Synonyms : [AZD2171]

Related Terms : [Recentin]

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  • 5 mg
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  • 200 mg
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  • 300 mg
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  • M.W. 450.51
  • C25H27FN4O3
  • [288383-20-0]

Storage: Store at or below -20 ºC. Solubility: Soluble in DMSO. Disposal: A.

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  • Cediranib is a highly potent inhibitor of recombinant KDR tyrosine kinase activity in vitro (IC50 < 1 nM). Inhibitory activity was also observed against the kinase associated with Flt-1 (IC50 = 5 nM), the VEGF-C and VEGF-D receptor Flt-4 (IC50 ≤ 3 nM), recombinant PDGFR-related kinase c-Kit (IC50 = 2 nM), and PDGFRβ tyrosine kinase (IC50 = 5 nM). In HUVEC, it inhibited VEGF-stimulated phosphorylation of KDR, c-Kit, PDGFR-α, PDGFR-β in a dose-dependent manner with IC50 values of 0.5, 1, 5, and 8 nM, respectively. It inhibited VEGF-stimulated HUVEC proliferation potently with an IC50 value of 0.4 nM. Consistent with potent activity against VEGF signaling, cediranib inhibited vessel branching, length, and area in vitro with IC50 values of 0.1, 0.1, and 0.2 nM, respectively. It also completely abolished VEGF-induced angiogenesis in vivo. However, it inhibited tumor cell proliferation in vitro only at comparatively high concentrations, showing IC50 values of 3.0 µM for SKOV-3 cells, 3.8 µM for MDA-MB-231 cells, 5.8 µM for PC-3 cells, 6.4 µM for Calu-6 cells, and 7.4 µM for SW620 cells. It also inhibited the growth of these five tumor models in nude mice. Furthermore, cediranib induced vascular regression in human lung tumor xenografts. Wedge, S.R., et al. "AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer." Cancer Res. 65: 4389-4400 (2005).
  • Cediranib significantly increased survival of mice wth glioblastoma by decreasing tumor vessel permeability, normalizing perivascular cell coverage, and thinning of the basement membrane, thus controlling edema. Kamoun, W.S., et al. "Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice." J. Clin. Oncol. 27: 2542-2552 (2009).
  • Hypertension induced by cediranib is reported to be manageable. Langenberg, M.H., et al. "Effective strategies for management of hypertension after vascular endothelial growth factor signaling inhibition therapy: results from a phase II randomized, factorial, double-blind study of Cediranib in patients with advanced solid tumors." J. Clin. Oncol. 27: 6152-6159 (2009).
  • Cediranib demonstrated potent antitumor and antiangiogenic efficacy in the murine renal cell carcinoma model. Medinger, M., et al. "Antitumor and antiangiogenic activity of cediranib in a preclinical model of renal cell carcinoma." Anticancer Res. 29: 5065-5076 (2009).
  • Combined treatments of cediranib with radiation in Calu-6 lung xenografts induced a significantly enhanced growth delay when compared with either modality alone. Williams, K.J., et al. "Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTIN; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts." Br. J. Radiol. 81: S21-S27 (2008).
  • Cediranib reverses ABCB1 (P-glycoprotein)- and ABCC1 (MRP1)-mediated multidrug resistance by directly inhibiting their drug efflux function. Tao, L.Y., et al. "Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function." Cancer Chemother. Pharmacol. 64: 961-969 (2009).
  • Related CAS numbers: 857036-77-2 for the cediranib maleate
  • Other CAS numbers previously assigned to cediranib, namely 557795-03-6 and 790713-41-6, have been deleted by CAS and are no longer in use.
  • Cediranib is the active ingredient in the drug product sold under the trade name Recentin®.  This drug is currently approved in at least one country for use in patients with non-small cell lung cancer, small cell lung cancer, kidney cancer, colorectal cancer, breast cancer, liver and ovarian cancer, melanoma, mesothelioma, and glioblastoma.  NOTE: THE CEDIRANIB SOLD BY LC LABORATORIES FOR RESEARCH IS NOT RECENTIN®, AND IS NOT FOR HUMAN USE.
  • Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
  • This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
  • Not available in some countries; not available to some institutions; not available for some uses.