Zibotentan (ZD4054 )

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WARNING: This product is for research use only, not for human or veterinary use.

Description:An orally available selective antagonist of the endothelin-A (ET-A) receptor with potential antineoplastic activity. Zibotentan binds selectively to the ET-A receptor, thereby inhibiting endothelin-mediated mechanisms that promote tumor cell proliferation.

Price and Availability

Zibotentan, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 203200Name: Zibotentan (ZD4054 )CAS#: 186497-07-4Chemical Formula: C19H16N6O4SExact Mass: 424.09537Molecular Weight: 424.43Elemental Analysis:C, 53.77; H, 3.80; N, 19.80; O, 15.08; S, 7.55

Synonym:ZD4054; ZD-4054; ZD 4054; Zibotentan.

IUPAC/Chemical Name:2-(4-(1,3,4-oxadiazol-2-yl)phenyl)-N-(3-methoxy-5-methylpyrazin-2-yl)pyridine-3-sulfonamide

InChi Key:FJHHZXWJVIEFGJ-UHFFFAOYSA-N

InChi Code:InChI=1S/C19H16N6O4S/c1-12-10-21-17(19(23-12)28-2)25-30(26,27)15-4-3-9-20-16(15)13-5-7-14(8-6-13)18-24-22-11-29-18/h3-11H,1-2H3,(H,21,25)

SMILES Code:O=S(C1=CC=CN=C1C2=CC=C(C3=NN=CO3)C=C2)(NC4=NC=C(C)N=C4OC)=O

Technical Data

Additional Information

 ZD4054 is a specific ETA receptor antagonist currently being evaluated in hormone-resistant prostate cancer in phase III clinical trials. In vitro, ZD4054 reversed ET-1-mediated inhibition of apoptosis in serum-deprived rat A10 and human VLTR-16 cells in a concentration-dependent manner. ZD4054 inhibited ET-1-mediated survival signaling pathways and decreased proliferation in ovarian OVCA 433 and HEY cells and in prostate PPC-1 and LAPC-4 cells. In A673 rhabdomyosarcoma cells, ET-1-induced phosphorylation of FAK, FAK, and paxillin was reversed with ZD4054, inhibiting the invasive phenotype mediated by these adhesion factors. In vivo, ZD4054 led to a significant reduction in tumor growth in animals bearing ovarian tumor xenografts, and significantly inhibited tumor angiogenesis. Pretreatment with ZD4054 also significantly delayed the onset of metastatic events after intracardiac injection of bladder TSU-Pr1-B1 cells in mice. These preclinical data show the potential anticancer effects of the specific blockade of the ETA receptor with ZD4054, supporting a program of clinical investigation. see http://www.ncbi.nlm.nih.gov/pubmed/19065106.    

References

 1: Dawson N, Payne H, Battersby C, Taboada M,James N. Health-related quality of life in pain-free or mildlysymptomatic patients with metastatic hormone-resistant prostate cancerfollowing treatment with the specific endothelin A receptor antagonistzibotentan (ZD4054). J Cancer Res Clin Oncol. 2010 Apr 14. [Epub aheadof print] PubMed PMID: 20390429.

2: Albiges L, Loriot Y, Gross-Goupil M, de La Motte Rouge T, Blesius A,Escudier B, Massard C, Fizazi K. [New drugs in metastaticcastration-resistant prostate cancer]. Bull Cancer. 2010Jan;97(1):149-59. French. PubMed PMID: 20022854.

3: Smollich M, Götte M, Fischgräbe J, Macedo LF, Brodie A, Chen S, RadkeI, Kiesel L, Wülfing P. ETAR antagonist ZD4054 exhibits additive effectswith aromatase inhibitors and fulvestrant in breast cancer therapy, andimproves in vivo efficacy of anastrozole. Breast Cancer Res Treat. 2009Nov 27. [Epub ahead of print] PubMed PMID: 19943105.

4: Schelman WR, Liu G, Wilding G, Morris T, Phung D, Dreicer R. A phaseI study of zibotentan (ZD4054) in patients with metastatic,castrate-resistant prostate cancer. Invest New Drugs. 2009 Sep 19. [Epubahead of print] PubMed PMID: 19763400.

5: Fizazi K, Miller K. Specific endothelin-A receptor antagonism for thetreatment of advanced prostate cancer. BJU Int. 2009 Nov;104(10):1423-5.Epub 2009 Jul 14. PubMed PMID: 19624592.

6: Swaisland HC, Oliver SD, Morris T, Jones HK, Bakhtyari A, Mackey A,McCormick AD, Slamon D, Hargreaves JA, Millar A, Taboada MT. In vitrometabolism of the specific endothelin-A receptor antagonist ZD4054 andclinical drug interactions between ZD4054 and rifampicin or itraconazolein healthy male volunteers. Xenobiotica. 2009 Jun;39(6):444-56. PubMedPMID: 19480550.

7: Rosanò L, Cianfrocca R, Masi S, Spinella F, Di Castro V, Biroccio A,Salvati E, Nicotra MR, Natali PG, Bagnato A. Beta-arrestin linksendothelin A receptor to beta-catenin signaling to induce ovarian cancercell invasion and metastasis. Proc Natl Acad Sci U S A. 2009 Feb24;106(8):2806-11. Epub 2009 Feb 6. PubMed PMID: 19202075; PubMedCentral PMCID: PMC2650347.

8: Growcott JW. Preclinical anticancer activity of the specificendothelin A receptor antagonist ZD4054. Anticancer Drugs. 2009Feb;20(2):83-8. Review. PubMed PMID: 19065106.

9: James ND, Caty A, Borre M, Zonnenberg BA, Beuzeboc P, Morris T, PhungD, Dawson NA. Safety and efficacy of the specific endothelin-A receptorantagonist ZD4054 in patients with hormone-resistant prostate cancer andbone metastases who were pain free or mildly symptomatic: adouble-blind, placebo-controlled, randomised, phase 2 trial. Eur Urol.2009 May;55(5):1112-23. Epub 2008 Nov 29. PubMed PMID: 19042080.

10: Warren R, Liu G. ZD4054: a specific endothelin A receptor antagonistwith promising activity in metastatic castration-resistant prostatecancer. Expert Opin Investig Drugs. 2008 Aug;17(8):1237-45. Review.PubMed PMID: 18616419.