Cediranib

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Cediranib
AZD2171.svg
Systematic (IUPAC) name
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
Clinical data
Legal status ?
Routes Oral
Pharmacokinetic data
Half-life 12 to 35 hours
Identifiers
CAS number 288383-20-0 YesY
ATC code None
PubChem CID 9933475
ChemSpider 8109103 N
UNII NQU9IPY4K9 YesY
ChEMBL CHEMBL491473 N
Chemical data
Formula C25H27FN4O3 
Mol. mass 450.505 g/mol
 N (what is this?)  (verify)

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.

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] As of November 2012, it was being assessed in double-blind studies for the treatment of methylated Glioblastoma Multiforme at the University of Washington Medical Center at a 20 mg daily dose.

Combination Trials[edit]

Findings from a federally funded, NCI-sponsored phase II clinical trial[5] presented at the 50th Annual Meeting of the American Society of Clinical Oncology (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),[6] show that the combination of two investigational oral drugs, olaparib (AZD-2281; AstraZeneca) , a potential first-in-class poly ADP ribose polymerase or PARP inhibitor and cediranib (AZD-2171; AstraZeneca), an anti-angiogenesis drug, is significantly more active against recurrent, platinum chemotherapy-sensitive disease or ovarian cancer related to mutations in BRCA genes than olaparib alone.[7]

References[edit]

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