CAS#: 288383-20-0 (free base)
Description: Cediranib is an indole ether quinazoline derivative with antineoplastic activities. Competing with adenosine triphosphate, cediranib binds to and inhibits all three vascular endothelial growth factor receptor (VEGF-1,-2,-3) tyrosine kinases, thereby blocking VEGF-signaling, angiogenesis, and tumor cell growth.
Synonym: AZD2171; AZD 2171; AZD-2171; Cediranib; US brand name: Recentin. Foreign brand name: Recentin.
IUPAC/Chemical Name: 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline
CAS#: 288383-20-0 (free base)
Chemical Formula: C25H27FN4O3
Exact Mass: 450.20672
Molecular Weight: 450.5
Elemental Analysis: C, 66.65; H, 6.04; F, 4.22; N, 12.44; O, 10.65.
According to http://en.wikipedia.org/wiki/Cediranib, Cediranib is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. It is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration. Beginning in 2007, it is undergoing Phase I clinical trials for the treatment of non-small cell lung cancer, kidney cancer, and colorectal cancer in adults, as well as tumors of the central nervous system in children. Phase I trials of interactions with other drugs used in cancer treatment are also underway. On February 27, 2008, AstraZeneca announced that the use of Recentin in non-small cell lung cancer will not progress into phase III after failing to meet its main goal. On 8th March 2010, AstraZeneca issued a press-release stating that Recentin had failed Phase III clinical trials for use in first-line metastatic colorectal cancer when it was compared clinically with the market-leader Avastin.
1: Morelli MP, Brown AM, Pitts TM, Tentler JJ, Ciardiello F, Ryan A, JÃ¼rgensmeier JM, Eckhardt SG. Targeting vascular endothelial growth factor receptor-1 and -3 with cediranib (AZD2171): effects on migration and invasion of gastrointestinal cancer cell lines. Mol Cancer Ther. 2009 Sep;8(9):2546-58. Epub 2009 Sep 15. PubMed PMID: 19755510; PubMed Central PMCID: PMC2819052.
2: Tao LY, Liang YJ, Wang F, Chen LM, Yan YY, Dai CL, Fu LW. Cediranib (recentin, AZD2171) reverses ABCB1- and ABCC1-mediated multidrug resistance by inhibition of their transport function. Cancer Chemother Pharmacol. 2009 Oct;64(5):961-9. Epub 2009 Mar 3. PubMed PMID: 19255759.
3: Siemann DW, Brazelle WD, JÃ¼rgensmeier JM. The vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor cediranib (Recentin; AZD2171) inhibits endothelial cell function and growth of human renal tumor xenografts. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):897-903. PubMed PMID: 19215823; PubMed Central PMCID: PMC2788500.
4: Robertson JD, Botwood NA, Rothenberg ML, Schmoll HJ. Phase III trial of FOLFOX plus bevacizumab or cediranib (AZD2171) as first-line treatment of patients with metastatic colorectal cancer: HORIZON III. Clin Colorectal Cancer. 2009 Jan;8(1):59-60. PubMed PMID: 19203899.
5: Williams KJ, Telfer BA, Shannon AM, Babur M, Stratford IJ, Wedge SR. 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. 2008 Oct;81 Spec No 1:S21-7. PubMed PMID: 18819995.
6: Bradley DP, Tessier JJ, Lacey T, Scott M, JÃ¼rgensmeier JM, Odedra R, Mills J, Kilburn L, Wedge SR. Examining the acute effects of cediranib (RECENTIN, AZD2171) treatment in tumor models: a dynamic contrast-enhanced MRI study using gadopentate. Magn Reson Imaging. 2009 Apr;27(3):377-84. Epub 2008 Sep 23. PubMed PMID: 18814988.
7: Curwen JO, Musgrove HL, Kendrew J, Richmond GH, Ogilvie DJ, Wedge SR. Inhibition of vascular endothelial growth factor-a signaling induces hypertension: examining the effect of cediranib (recentin; AZD2171) treatment on blood pressure in rat and the use of concomitant antihypertensive therapy. Clin Cancer Res. 2008 May 15;14(10):3124-31. PubMed PMID: 18483380.
8: Laurie SA, Gauthier I, Arnold A, Shepherd FA, Ellis PM, Chen E, Goss G, Powers J, Walsh W, Tu D, Robertson J, Puchalski TA, Seymour L. Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institute of Canada clinical trials group. J Clin Oncol. 2008 Apr 10;26(11):1871-8. PubMed PMID: 18398152.
9: Smith NR, James NH, Oakley I, Wainwright A, Copley C, Kendrew J, Womersley LM, JÃ¼rgensmeier JM, Wedge SR, Barry ST. Acute pharmacodynamic and antivascular effects of the vascular endothelial growth factor signaling inhibitor AZD2171 in Calu-6 human lung tumor xenografts. Mol Cancer Ther. 2007 Aug;6(8):2198-208. PubMed PMID: 17699717.
10: Hanrahan EO, Heymach JV. Vascular endothelial growth factor receptor tyrosine kinase inhibitors vandetanib (ZD6474) and AZD2171 in lung cancer. Clin Cancer Res. 2007 Aug 1;13(15 Pt 2):s4617-22. Review. PubMed PMID: 17671152.