Cediranib: Difference between revisions

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{{Short description|Chemical compound}}
{{Drugbox
{{Drugbox
| Verifiedfields = changed
| Verifiedfields = changed
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| verifiedrevid = 449572361
| verifiedrevid = 449572361
| IUPAC_name = 4-[(4-fluoro-2-methyl-1''H''-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
| IUPAC_name = 4-[(4-fluoro-2-methyl-1''H''-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
| image = AZD2171.svg
| image = Cediranib.svg
<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename =
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category =
| pregnancy_category =
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S8 -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| legal_status =
| routes_of_administration = Oral
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
<!--Pharmacokinetic data-->
| bioavailability =
| bioavailability =
| protein_bound =
| protein_bound =
| metabolism =
| metabolism =
| elimination_half-life = 12 to 35 hours
| elimination_half-life = 12 to 35 hours
| excretion =
| excretion =
<!--Identifiers-->
<!--Identifiers-->
| IUPHAR_ligand = 5664
| IUPHAR_ligand = 5664
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| CAS_number = 288383-20-0
| CAS_number = 288383-20-0
| ATC_prefix = L01
| ATC_prefix = L01
| ATC_suffix = XE32
| ATC_suffix = EK02
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| DrugBank =
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NQU9IPY4K9
| UNII = NQU9IPY4K9
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 8109103
| ChemSpiderID = 8109103
| KEGG = D08881
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChI = 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
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<!--Chemical data-->
<!--Chemical data-->
| C=25 | H=27 | F=1 | N=4 | O=3
| C=25 | H=27 | F=1 | N=4 | O=3
| smiles = COc4cc3c(Oc2ccc1[nH]c(C)cc1c2F)ncnc3cc4OCCCN5CCCC5
| molecular_weight = 450.505 g/mol
| smiles = Cc4nc5ccc(Oc3ncnc2cc(OCCCN1CCCC1)c(OC)cc23)c(F)c5c4
}}
}}
'''Cediranib''' (AZD-2171; tentative trade name '''Recentin''') is a potent [[kinase inhibitor|inhibitor]] of [[vascular endothelial growth factor]] (VEGF) receptor [[tyrosine kinase]]s.<ref name="pmid15899831">{{cite journal |author=Wedge SR, Kendrew J, Hennequin LF |title=AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer |journal=Cancer Res. |volume=65 |issue=10 |pages=4389–400 |date=May 2005 |pmid=15899831 |doi=10.1158/0008-5472.CAN-04-4409 |url=http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15899831|display-authors=etal}}</ref><ref name="pmid19091548">{{cite journal |author=Goss G, Shepherd FA, Laurie S |title=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 |journal=Eur. J. Cancer |volume= 45|issue= 5|pages= 782–8|date=December 2008 |pmid=19091548 |doi=10.1016/j.ejca.2008.10.022 |url=http://linkinghub.elsevier.com/retrieve/pii/S0959-8049(08)00868-X|display-authors=etal}}</ref><ref name="pmid18520296">{{cite journal |author=Nikolinakos P, Heymach JV |title=The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies |journal=J Thorac Oncol |volume=3 |issue=6 Suppl 2 |pages=S131–4 |date=June 2008 |pmid=18520296 |doi=10.1097/JTO.0b013e318174e910 |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?doi=10.1097/JTO.0b013e318174e910}}</ref>
'''Cediranib''' (AZD-2171; tentative trade name '''Recentin''') is a potent [[kinase inhibitor|inhibitor]] of [[vascular endothelial growth factor]] (VEGF) receptor [[tyrosine kinase]]s.<ref name="pmid15899831">{{cite journal | vauthors = Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, Chester R, Jackson JA, Boffey SJ, Kilburn LL, Barnett S, Richmond GH, Wadsworth PF, Walker M, Bigley AL, Taylor ST, Cooper L, Beck S, Jürgensmeier JM, Ogilvie DJ | display-authors = 6 | title = AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer | journal = Cancer Research | volume = 65 | issue = 10 | pages = 4389–400 | date = May 2005 | pmid = 15899831 | doi = 10.1158/0008-5472.CAN-04-4409 | doi-access = free }}</ref><ref name="pmid19091548">{{cite journal | vauthors = Goss G, Shepherd FA, Laurie S, Gauthier I, Leighl N, Chen E, Feld R, Powers J, Seymour L | display-authors = 6 | title = 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 | journal = European Journal of Cancer | volume = 45 | issue = 5 | pages = 782–8 | date = March 2009 | pmid = 19091548 | doi = 10.1016/j.ejca.2008.10.022 }}</ref><ref name="pmid18520296">{{cite journal | vauthors = Nikolinakos P, Heymach JV | title = The tyrosine kinase inhibitor cediranib for non-small cell lung cancer and other thoracic malignancies | journal = Journal of Thoracic Oncology | volume = 3 | issue = 6 Suppl 2 | pages = S131-4 | date = June 2008 | pmid = 18520296 | doi = 10.1097/JTO.0b013e318174e910 | doi-access = free }}</ref>


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


== Clinical trials ==
Beginning in 2007, it underwent [[Clinical trial#Phase I|Phase I]] [[clinical trial]]s for the treatment of [[Lung cancer#Non-small cell lung cancer|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.
Beginning in 2007, it underwent [[Clinical trial#Phase I|phase I]] [[clinical trial]]s for the treatment of [[Lung cancer#Non-small cell lung cancer|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.{{cn|date=February 2023}}


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]].<ref>{{cite web|title=AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer|url=http://www.astrazeneca.com/Media/Press-releases/Article/20100308--RECENTIN-did-not-meet-primary-endpoint-in-Horizon-III|accessdate=17 March 2014}}</ref> 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&nbsp;mg daily dose.
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]].<ref>{{cite web|title=AstraZeneca - RECENTIN did not meet primary endpoint in Horizon III study in metastatic colorectal cancer|url=http://www.astrazeneca.com/Media/Press-releases/Article/20100308--RECENTIN-did-not-meet-primary-endpoint-in-Horizon-III|access-date=17 March 2014}}</ref>
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.<ref>{{cite journal | vauthors = Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, Mason W, Mikkelsen T, Phuphanich S, Ashby LS, Degroot J, Gattamaneni R, Cher L, Rosenthal M, Payer F, Jürgensmeier JM, Jain RK, Sorensen AG, Xu J, Liu Q, van den Bent M | display-authors = 6 | title = Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma | journal = Journal of Clinical Oncology | volume = 31 | issue = 26 | pages = 3212–8 | date = September 2013 | pmid = 23940216 | pmc = 4021043 | doi = 10.1200/JCO.2012.47.2464 | authorlink8 = Tom Mikkelsen }}</ref>


==Combination trials==
==Combination trials==
Findings from a federally funded, NCI-sponsored phase II clinical trial<ref>{{cite web|title=Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, Peritoneal Cancer, or Triple-Negative Breast Cancer|url=http://clinicaltrials.gov/show/NCT01116648|accessdate=12 June 2014}}</ref> presented at the 50th Annual Meeting of the [[American Society of Clinical Oncology]] (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),<ref>[http://abstracts.asco.org/144/AbstView_144_130933.html 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)])</ref> 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.<ref>[http://oncozine.com/profiles/blogs/combination-of-targeted-drugs-may-significantly-increase-pfs 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]</ref>
Findings from a federally funded, NCI-sponsored phase II clinical trial<ref>{{ClinicalTrialsGov|NCT01116648|Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer}}</ref> presented at the 50th Annual Meeting of the [[American Society of Clinical Oncology]] (May 30 - June 3, 2014, Chicago, Ill; Abstract No: LBA5500),<ref>{{cite journal | vauthors = Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, Luo W, Quy P, Whalen C, Obermayer L, Lee H, Winer EP, Kohn EC, Ivy SP, Matulonis UA | display-authors = 6 | title = Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study | journal = The Lancet. Oncology | volume = 15 | issue = 11 | pages = 1207–14 | date = October 2014 | pmid = 25218906 | pmc = 4294183 | doi = 10.1016/S1470-2045(14)70391-2 }}</ref> 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.<ref>{{Cite web |url=http://oncozine.com/profiles/blogs/combination-of-targeted-drugs-may-significantly-increase-pfs |title=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 |access-date=June 12, 2014 |archive-url=https://web.archive.org/web/20150221153623/http://oncozine.com/profiles/blogs/combination-of-targeted-drugs-may-significantly-increase-pfs |archive-date=February 21, 2015 |url-status=dead }}</ref>


==References==
== References ==
{{reflist}}
{{reflist}}


==External links==
== External links ==
*[http://www.cancerline.com/cancerlinehcp/15602_15632_9_3_1.aspx AZD2171&mdash;AstraZeneca Pipeline]
* [https://web.archive.org/web/20070310202726/http://www.cancerline.com/cancerlinehcp/15602_15632_9_3_1.aspx AZD2171—AstraZeneca Pipeline]


{{Extracellular chemotherapeutic agents}}
{{Extracellular chemotherapeutic agents}}
{{Growth factor receptor modulators}}


[[Category:Receptor tyrosine kinase inhibitors]]
[[Category:Receptor tyrosine kinase inhibitors]]
[[Category:Indoles]]
[[Category:Indole ethers at the benzene ring]]
[[Category:Quinazolines]]
[[Category:Quinazolines]]
[[Category:Drugs developed by AstraZeneca]]
[[Category:Fluoroarenes]]
[[Category:Fluoroarenes]]
[[Category:Phenol ethers]]
[[Category:Catechol ethers]]
[[Category:Pyrrolidines]]
[[Category:1-Pyrrolidinyl compounds]]
[[Category:Experimental cancer drugs]]
[[Category:Experimental cancer drugs]]

Latest revision as of 19:21, 20 December 2023

Cediranib
Clinical data
Routes of
administration		Oral
ATC code
Pharmacokinetic data
Elimination half-life12 to 35 hours
Identifiers
  • 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl)propoxy]quinazoline
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.196.628 Edit this at Wikidata
Chemical and physical data
FormulaC25H27FN4O3
Molar mass450.514 g·mol−1
3D model (JSmol)
  • COc4cc3c(Oc2ccc1[nH]c(C)cc1c2F)ncnc3cc4OCCCN5CCCC5
  • 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 ☒N
  • Key:XXJWYDDUDKYVKI-UHFFFAOYSA-N ☒N
 ☒NcheckY (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.

Clinical trials[edit]

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.[citation needed]

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[edit]

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[edit]

  1. ^ Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, 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 Research. 65 (10): 4389–400. doi:10.1158/0008-5472.CAN-04-4409. PMID 15899831.
  2. ^ Goss G, Shepherd FA, Laurie S, Gauthier I, Leighl N, Chen E, et al. (March 2009). "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". European Journal of 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". Journal of Thoracic Oncology. 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. ^ Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Wick A, et al. (September 2013). "Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma". Journal of Clinical Oncology. 31 (26): 3212–8. doi:10.1200/JCO.2012.47.2464. PMC 4021043. PMID 23940216.
  6. ^ Clinical trial number NCT01116648 for "Cediranib Maleate and Olaparib in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Peritoneal Cancer or Recurrent Triple-Negative Breast Cancer" at ClinicalTrials.gov
  7. ^ Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, et al. (October 2014). "Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study". The Lancet. Oncology. 15 (11): 1207–14. doi:10.1016/S1470-2045(14)70391-2. PMC 4294183. PMID 25218906.
  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". Archived from the original on February 21, 2015. Retrieved June 12, 2014.

External links[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Cediranib&oldid=1190942479"