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

THEORETICAL ANALYSIS

Name: Cediranib
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.

TECHNICAL DATA

ADDITIONAL INFORMATION

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.

REFERENCES

1: Morelli MP, Brown AM, Pitts TM, Tentler JJ, Ciardiello F, Ryan A, Jürgensmeier 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, Jürgensmeier 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, Jürgensmeier 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, Jürgensmeier 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.