Cediranib free base
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MedKoo CAT#: 200690

CAS#: 288383-20-0 (free base)

Description: Cediranib, also known as AZD-2171, is a potent and selective VEGF inhibitor 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.


Chemical Structure

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Cediranib free base
CAS# 288383-20-0 (free base)

Theoretical Analysis

MedKoo Cat#: 200690
Name: Cediranib free base
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.

Price and Availability

Size Price Availability Quantity
50.0mg USD 150.0 2 Weeks
100.0mg USD 250.0 2 Weeks
200.0mg USD 450.0 2 Weeks
500.0mg USD 950.0 2 Weeks
1.0g USD 1650.0 2 Weeks
2.0g USD 2950.0 2 Weeks
5.0g USD 4950.0 2 Weeks
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Related CAS #: 857036-77-2 (maleate)   288383-20-0 (free base)    

Synonym: AZD2171; AZD 2171; AZD-2171; AZD2171 free base; Cediranib; brand name: Recentin.

IUPAC/Chemical Name: 4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline

InChi Key: XXJWYDDUDKYVKI-UHFFFAOYSA-N

InChi Code: 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

SMILES Code: COC1=CC2=C(OC3=C(F)C4=C(NC(C)=C4)C=C3)N=CN=C2C=C1OCCCN5CCCC5

Appearance: white solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: Cediranib (AZD2171) is a highly potent, orally available VEGFR tyrosine kinase inhibitor with IC50s of <1, <3, 5, 5, 36, 2 nM for Flt1, KDR, Flt4, PDGFRα, PDGFRβ, c-Kit, respectively.
In vitro activity: Data demonstrated that the expression of VEGFR2 and VEGFR3 was consistently downregulated after CED (Cediranib) treatment (Figures 6(a) and 6(b)). Phosphorylated Akt (p-Akt), phosphorylated p38 (p-p38), and phosphorylated mTOR (p-mTOR) were also inhibited by CED in all doses while phosphorylated Erk1/2 (p-Erk1/2) was only significantly decreased in the 9 μM group (Figures 6(c) and 6(d)). In addition, p38, Erk1/2, and mTOR had no change in all groups. Meanwhile, this study found that CED can reduce Akt expression in the 6 μM group and the 9 μM group. These data suggested that CED may induce autophagy and G1 phase cell cycle arrest through suppressing MAPK and Akt/mTOR signal pathways. Reference: Biomed Res Int. 2021; 2021: 5582648. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024085/
In vivo activity: In tumor xenografts, cediranib treatment increases hypoxia, and HDR gene expression is reduced in hypoxic cells isolated from tumors. This study therefore proposes two mechanisms by which cediranib impairs HDR in tumors: (i) a direct effect via PDGFR inhibition that suppresses DNA repair gene expression through PP2A activation and E2F4/p130 occupancy of the HDR gene promoters and (ii) an indirect effect via VEGFR2-mediated inhibition of angiogenesis, causing decreased perfusion and increased hypoxia, which secondarily suppresses HDR gene expression (Fig. 7I). Reference: Sci Transl Med. 2019 May 15; 11(492): eaav4508. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626544/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 44.39

Preparing Stock Solutions

The following data is based on the product molecular weight 450.5 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
In vitro protocol: 1. Guo M, Liu Z, Si J, Zhang J, Zhao J, Guo Z, Xie Y, Zhang H, Gan L. Cediranib Induces Apoptosis, G1 Phase Cell Cycle Arrest, and Autophagy in Non-Small-Cell Lung Cancer Cell A549 In Vitro. Biomed Res Int. 2021 Mar 29;2021:5582648. doi: 10.1155/2021/5582648. PMID: 33860036; PMCID: PMC8024085. 2. 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. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. doi: 10.1158/0008-5472.CAN-04-4409. PMID: 15899831.
In vivo protocol: 1. Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, Glazer PM. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Sci Transl Med. 2019 May 15;11(492):eaav4508. doi: 10.1126/scitranslmed.aav4508. PMID: 31092693; PMCID: PMC6626544. 2. Jiang Y, Allen D, Kersemans V, Devery AM, Bokobza SM, Smart S, Ryan AJ. Acute vascular response to cediranib treatment in human non-small-cell lung cancer xenografts with different tumour stromal architecture. Lung Cancer. 2015 Nov;90(2):191-8. doi: 10.1016/j.lungcan.2015.08.009. Epub 2015 Aug 20. PMID: 26323213; PMCID: PMC4641245. 2. 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. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res. 2005 May 15;65(10):4389-400. doi: 10.1158/0008-5472.CAN-04-4409. PMID: 15899831.

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1: Al-Huniti N, Petersson K, Tang W, Masson E, Li J. Population exposure-safety analysis of cediranib for Phase I and II studies in patients with cancer. Br J Clin Pharmacol. 2017 Dec 22. doi: 10.1111/bcp.13495. [Epub ahead of print] PubMed PMID: 29274100.

2: Andronesi OC, Esmaeili M, Borra RJH, Emblem K, Gerstner ER, Pinho MC, Plotkin SR, Chi AS, Eichler AF, Dietrich J, Ivy SP, Wen PY, Duda DG, Jain R, Rosen BR, Sorensen GA, Batchelor TT. Early changes in glioblastoma metabolism measured by MR spectroscopic imaging during combination of anti-angiogenic cediranib and chemoradiation therapy are associated with survival. NPJ Precis Oncol. 2017;1. pii: 20. doi: 10.1038/s41698-017-0020-3. Epub 2017 Jun 12. PubMed PMID: 29202103; PubMed Central PMCID: PMC5708878.

3: Orbegoso C, Marquina G, George A, Banerjee S. The role of Cediranib in ovarian cancer. Expert Opin Pharmacother. 2017 Oct;18(15):1637-1648. doi: 10.1080/14656566.2017.1383384. PubMed PMID: 28933580.

4: Tsao AS, Moon J, Wistuba II, Vogelzang NJ, Kalemkerian GP, Redman MW, Gandara DR, Kelly K. Phase I Trial of Cediranib in Combination with Cisplatin and Pemetrexed in Chemonaive Patients with Unresectable Malignant Pleural Mesothelioma (SWOG S0905). J Thorac Oncol. 2017 Aug;12(8):1299-1308. doi: 10.1016/j.jtho.2017.05.021. Epub 2017 Jun 6. PubMed PMID: 28599887; PubMed Central PMCID: PMC5690479.

5: Lee JM, Cimino-Mathews A, Peer CJ, Zimmer A, Lipkowitz S, Annunziata CM, Cao L, Harrell MI, Swisher EM, Houston N, Botesteanu DA, Taube JM, Thompson E, Ogurtsova A, Xu H, Nguyen J, Ho TW, Figg WD, Kohn EC. Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. J Clin Oncol. 2017 Jul 1;35(19):2193-2202. doi: 10.1200/JCO.2016.72.1340. Epub 2017 May 4. PubMed PMID: 28471727; PubMed Central PMCID: PMC5493052.

6: Jiang W, Liu P, Li X, Wang P. Identification of target genes of cediranib in alveolar soft part sarcoma using a gene microarray. Oncol Lett. 2017 Apr;13(4):2623-2630. doi: 10.3892/ol.2017.5779. Epub 2017 Feb 24. PubMed PMID: 28454442; PubMed Central PMCID: PMC5403492.

7: Stark DP, Cook A, Brown JM, Brundage MD, Embleton AC, Kaplan RS, Raja FA, Swart AMW, Velikova G, Qian W, Ledermann JA. Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial. Cancer. 2017 Jul 15;123(14):2752-2761. doi: 10.1002/cncr.30657. Epub 2017 Mar 24. PubMed PMID: 28339098; PubMed Central PMCID: PMC5516140.

8: Li J, Al-Huniti N, Henningsson A, Tang W, Masson E. Population pharmacokinetic and exposure simulation analysis for cediranib (AZD2171) in pooled Phase I/II studies in patients with cancer. Br J Clin Pharmacol. 2017 Aug;83(8):1723-1733. doi: 10.1111/bcp.13266. Epub 2017 Mar 27. PubMed PMID: 28213941; PubMed Central PMCID: PMC5510068.

9: Melsens E, Verberckmoes B, Rosseel N, Vanhove C, Descamps B, Pattyn P, Ceelen W. The VEGFR Inhibitor Cediranib Improves the Efficacy of Fractionated Radiotherapy in a Colorectal Cancer Xenograft Model. Eur Surg Res. 2017;58(3-4):95-108. doi: 10.1159/000452741. Epub 2016 Dec 22. PubMed PMID: 28002822.

10: Tang W, McCormick A, Li J, Masson E. Clinical Pharmacokinetics and Pharmacodynamics of Cediranib. Clin Pharmacokinet. 2017 Jul;56(7):689-702. doi: 10.1007/s40262-016-0488-y. Review. PubMed PMID: 27943222.

11: Bordinhão AL, Evangelista AF, Oliveira RJ, Macedo T, Silveira HC, Reis RM, Marques MM. MicroRNA profiling in human breast cancer cell lines exposed to the anti-neoplastic drug cediranib. Oncol Rep. 2016 Dec;36(6):3197-3206. doi: 10.3892/or.2016.5153. Epub 2016 Oct 7. PubMed PMID: 27748845.

12: Brown N, McBain C, Nash S, Hopkins K, Sanghera P, Saran F, Phillips M, Dungey F, Clifton-Hadley L, Wanek K, Krell D, Jeffries S, Khan I, Smith P, Mulholland P. Multi-Center Randomized Phase II Study Comparing Cediranib plus Gefitinib with Cediranib plus Placebo in Subjects with Recurrent/Progressive Glioblastoma. PLoS One. 2016 May 27;11(5):e0156369. doi: 10.1371/journal.pone.0156369. eCollection 2016. PubMed PMID: 27232884; PubMed Central PMCID: PMC4883746.

13: Ledermann JA, Embleton AC, Raja F, Perren TJ, Jayson GC, Rustin GJS, Kaye SB, Hirte H, Eisenhauer E, Vaughan M, Friedlander M, González-Martín A, Stark D, Clark E, Farrelly L, Swart AM, Cook A, Kaplan RS, Parmar MKB; ICON6 collaborators. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Mar 12;387(10023):1066-1074. doi: 10.1016/S0140-6736(15)01167-8. Erratum in: Lancet. 2016 Apr 23;387(10029):1722. PubMed PMID: 27025186.

14: Drazin D, Al-Khouja L, Patel A, Hu J, Phuphanich S. Long-term Remission Over Six Years for a Patient with Recurrent Glioblastoma Treated with Cediranib/Lomustine. Cureus. 2016 Jan 16;8(1):e460. doi: 10.7759/cureus.460. PubMed PMID: 26929887; PubMed Central PMCID: PMC4757029.

15: Ivy SP, Liu JF, Lee JM, Matulonis UA, Kohn EC. Cediranib, a pan-VEGFR inhibitor, and olaparib, a PARP inhibitor, in combination therapy for high grade serous ovarian cancer. Expert Opin Investig Drugs. 2016;25(5):597-611. doi: 10.1517/13543784.2016.1156857. Epub 2016 Mar 16. Review. PubMed PMID: 26899229.

16: McWhirter E, Quirt I, Gajewski T, Pond G, Wang L, Hui J, Oza A. A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma. Invest New Drugs. 2016 Apr;34(2):231-5. doi: 10.1007/s10637-016-0324-0. Epub 2016 Feb 3. PubMed PMID: 26841902.

17: Powles T, Brown J, Larkin J, Jones R, Ralph C, Hawkins R, Chowdhury S, Boleti E, Bhal A, Fife K, Webb A, Crabb S, Geldart T, Hill R, Dunlop J, Hall PE, McLaren D, Ackerman C, Beltran L, Nathan P. A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK). Ann Oncol. 2016 May;27(5):880-6. doi: 10.1093/annonc/mdw014. Epub 2016 Jan 22. PubMed PMID: 26802156.

18: Ruscito I, Gasparri ML, Marchetti C, De Medici C, Bracchi C, Palaia I, Imboden S, Mueller MD, Papadia A, Muzii L, Panici PB. Cediranib in ovarian cancer: state of the art and future perspectives. Tumour Biol. 2016 Mar;37(3):2833-9. doi: 10.1007/s13277-015-4781-4. Epub 2016 Jan 11. Review. PubMed PMID: 26753963.

19: Lobo MR, Kukino A, Tran H, Schabel MC, Springer CS Jr, Gillespie GY, Grafe MR, Woltjer RL, Pike MM. Synergistic Antivascular and Antitumor Efficacy with Combined Cediranib and SC6889 in Intracranial Mouse Glioma. PLoS One. 2015 Dec 8;10(12):e0144488. doi: 10.1371/journal.pone.0144488. eCollection 2015. PubMed PMID: 26645398; PubMed Central PMCID: PMC4672903.

20: Tewari KS. Clinical implications for cediranib in advanced cervical cancer. Lancet Oncol. 2015 Nov;16(15):1447-8. doi: 10.1016/S1470-2045(15)00252-1. Epub 2015 Oct 22. PubMed PMID: 26474520.



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.