Cediranib

Cediranib
Clinical data
Routes of; administration	Oral
ATC code	L01XE32 (WHO) ;
Pharmacokinetic data
Elimination half-life	12 to 35 hours
Identifiers
	IUPAC name 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline;
CAS Number	288383-20-0 ;
PubChem CID	9933475;
IUPHAR/BPS	5664;
ChemSpider	8109103 ;
UNII	NQU9IPY4K9;
ChEMBL	ChEMBL491473 ;
CompTox Dashboard (EPA)	DTXSID10183035 ;
ECHA InfoCard	100.196.628
Chemical and physical data
Formula	C25H27FN4O3
Molar mass	450.505 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Cc4nc5ccc(Oc3ncnc2cc(OCCCN1CCCC1)c(OC)cc23)c(F)c5c4;
	InChI InChI=1S/C25H27FN4O3/c1-16-12-17-19(29-16)6-7-21(24(17)26)33-25-18-13-22(31-2)23(14-20(18)27-15-28-25)32-11-5-10-30-8-3-4-9-30/h6-7,12-15,29H,3-5,8-11H2,1-2H3 ; Key:XXJWYDDUDKYVKI-UHFFFAOYSA-N ;
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Cediranib (AZD-2171; tentative trade name Recentin) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases.^[1]^[2]^[3]

The drug is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration.

Clinical trials

Beginning in 2007, it underwent 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 were also undertaken.

On February 27, 2008, AstraZeneca announced that the use of cediranib in non-small cell lung cancer will not progress into phase III after failing to meet its main goal. On 8 March 2010, AstraZeneca issued a press-release stating that cediranib had failed Phase III clinical trials for use in first-line metastatic colorectal cancer when it was compared clinically with the market-leader bevacizumab.^[4] In 2016, AstraZeneca completed a phase III trial comparing the efficacy of cediranib alone and cediranib with lomustine to the efficacy of lomustine alone in patients with recurrent glioblastoma. The trial failed to meet its primary endpoint and survival was not extended with cediranib.^[5]

Combination trials

Findings from a federally funded, NCI-sponsored phase II clinical trial^[6] presented at the 50th Annual Meeting of the American Society of Clinical Oncology (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),^[7] show that the combination of two investigational oral drugs, olaparib, a PARP inhibitor, and cediranib is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes than olaparib alone.^[8]

References

^ Wedge SR, Kendrew J, Hennequin LF, et al. (May 2005). "AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer". Cancer Res. 65 (10): 4389–400. doi:10.1158/0008-5472.CAN-04-4409. PMID 15899831.
^ Goss G, Shepherd FA, Laurie S, et al. (December 2008). "A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: A study of the National Cancer Institute of Canada Clinical Trials Group". Eur. J. Cancer. 45 (5): 782–8. doi:10.1016/j.ejca.2008.10.022. PMID 19091548.
^ Nikolinakos P, Heymach JV (June 2008). "The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies". J Thorac Oncol. 3 (6 Suppl 2): S131–4. doi:10.1097/JTO.0b013e318174e910. PMID 18520296.
^ "AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer". Retrieved 17 March 2014.
^ https://www.ncbi.nlm.nih.gov/pubmed/23940216
^ "Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, Peritoneal Cancer, or Triple-Negative Breast Cancer". Retrieved 12 June 2014.
^ Liu J, Barry WT, Birrer MJ, et al. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer; J Clin Oncol 32:5s, 2014 (suppl; abstr LBA5500))
^ Combination of Targeted Drugs May Significantly Increase Progression-Free Survival in Women with Recurrent Ovarian Cancer, Study Shows - Onco'Zine - The International Oncology Network; June 2, 2014

External links

AZD2171—AstraZeneca Pipeline

[pmid15899831-1] Wedge SR, Kendrew J, Hennequin LF, et al. (May 2005). "AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer". Cancer Res. 65 (10): 4389–400. doi:10.1158/0008-5472.CAN-04-4409. PMID 15899831.

[pmid19091548-2] Goss G, Shepherd FA, Laurie S, et al. (December 2008). "A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: A study of the National Cancer Institute of Canada Clinical Trials Group". Eur. J. Cancer. 45 (5): 782–8. doi:10.1016/j.ejca.2008.10.022. PMID 19091548.

[pmid18520296-3] Nikolinakos P, Heymach JV (June 2008). "The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies". J Thorac Oncol. 3 (6 Suppl 2): S131–4. doi:10.1097/JTO.0b013e318174e910. PMID 18520296.

[4] "AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer". Retrieved 17 March 2014.

[5] ttps://www.ncbi.nlm.nih.gov/pubmed/23940216

[6] "Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, Peritoneal Cancer, or Triple-Negative Breast Cancer". Retrieved 12 June 2014.

[7] Liu J, Barry WT, Birrer MJ, et al. A randomized phase 2 trial comparing efficacy of the combination of the PARP inhibitor olaparib and the antiangiogenic cediranib against olaparib alone in recurrent platinum-sensitive ovarian cancer; J Clin Oncol 32:5s, 2014 (suppl; abstr LBA5500))

[8] Combination of Targeted Drugs May Significantly Increase Progression-Free Survival in Women with Recurrent Ovarian Cancer, Study Shows - Onco'Zine - The International Oncology Network; June 2, 2014

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