AZD-6126

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

Description:AZD6126, also known as ANG-453, a water-soluble phosphate prodrug of N-acetylcolchinol with potential antiangiogenesis and antineoplastic activities. AZD-6126 is an angiogenesis inhibitor and tubulin inhibitor potentially for the treatment of solid tumours. AZD6126 is converted in vivo into N-acetylcolchinol. N-acetylcolchinol binds to and destabilizes the tubulin cytoskeleton of endothelial cells in tumor blood vessels, which may result in tumor endothelial cel apoptosis, the selective occlusion of tumor blood vessels, cessation of tumor blood flow, and tumor necrosis.

Price and Availability

AZD-6126, purity > 98%,is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 200427Name: AZD-6126CAS#: 219923-05-4Chemical Formula: C20H24NO8PExact Mass: 437.12395Molecular Weight: 437.38Elemental Analysis:C, 54.92; H, 5.53; N, 3.20; O, 29.26; P, 7.08

Synonym:AZD6126; AZD 6126; AZD-6126; ANG453; ANG-453; ANG 453.

IUPAC/Chemical Name:(5S)-5-acetamido-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c][7]annulen-3-yl dihydrogen phosphate

InChi Key:UGBMEXLBFDAOGL-INIZCTEOSA-N

InChi Code:InChI=1S/C20H24NO8P/c1-11(22)21-16-8-5-12-9-17(26-2)19(27-3)20(28-4)18(12)14-7-6-13(10-15(14)16)29-30(23,24)25/h6-7,9-10,16H,5,8H2,1-4H3,(H,21,22)(H2,23,24,25)/t16-/m0/s1

SMILES Code:O=P(O)(OC1=CC=C(C2=C(OC)C(OC)=C(OC)C=C2CC[C@@H]3NC(C)=O)C3=C1)O

Technical Data

Additional Information

A phase I clinical trial identified gastrointestinal and cardiac effects as limiting dosing. Two phase II clinical trials were started investigating ZD6126 in metastatic renal cell carcinoma and metastatic colorectal cancer.ZD6126 was being investigated by AstraZeneca as a VDA (vascular disrupting agent). However, the trials were halted, after it became apparent that ZD6126 was too cardiotoxic at the required doses. [source: http://en.wikipedia.org/wiki/ZD6126].    

References

  1: Eichhorn ME, Klotz LV, Luedemann S, StriethS, Kleespies A, Preissler G, Lindner M, Jauch KW, Reiser MF, Clevert DA.Vascular targeting tumor therapy: Non-invasive contrast enhancedultrasound for quantitative assessment of tumor microcirculation. CancerBiol Ther. 2010 May 8;9(10). [Epub ahead of print] PubMed PMID:20234173.

2: Wang H, Li J, Chen F, De Keyzer F, Yu J, Feng Y, Nuyts J, Marchal G,Ni Y. Morphological, functional and metabolic imaging biomarkers:assessment of vascular-disrupting effect on rodent liver tumours. EurRadiol. 2010 Aug;20(8):2013-26. Epub 2010 Feb 25. PubMed PMID: 20182730.

3: Elice F, Rodeghiero F, Falanga A, Rickles FR. Thrombosis associatedwith angiogenesis inhibitors. Best Pract Res Clin Haematol. 2009Mar;22(1):115-28. Review. PubMed PMID: 19285278.

4: Fens MH, Hill KJ, Issa J, Ashton SE, Westwood FR, Blakey DC, Storm G,Ryan AJ, Schiffelers RM. Liposomal encapsulation enhances the antitumourefficacy of the vascular disrupting agent ZD6126 in murine B16.F10melanoma. Br J Cancer. 2008 Oct 21;99(8):1256-64. Epub 2008 Sep 16.PubMed PMID: 18797467; PubMed Central PMCID: PMC2570501.

5: Valentini G, D"Andrea C, Ferrari R, Pifferi A, Cubeddu R, MartinelliM, Natoli C, Ubezio P, Giavazzi R. In vivo measurement of vascularmodulation in experimental tumors using a fluorescent contrast agent.Photochem Photobiol. 2008 Sep-Oct;84(5):1249-56. Epub 2008 Apr 12.PubMed PMID: 18422875.

6: Partridge EA, D"Souza RA, Lenz EM, Smith SM, Clarkson-Jones J,Roberts DW. Disposition and metabolism of the colchicine derivative[14C]-ZD6126 in rat and dog. Xenobiotica. 2008 Apr;38(4):399-421. PubMedPMID: 18340564.

7: Cai SX. Small molecule vascular disrupting agents: potential newdrugs for cancer treatment. Recent Pat Anticancer Drug Discov. 2007Jan;2(1):79-101. Review. PubMed PMID: 18221055.

8: LoRusso PM, Gadgeel SM, Wozniak A, Barge AJ, Jones HK, DelPropostoZS, DeLuca PA, Evelhoch JL, Boerner SA, Wheeler C. Phase I clinicalevaluation of ZD6126, a novel vascular-targeting agent, in patients withsolid tumors. Invest New Drugs. 2008 Apr;26(2):159-67. Epub 2008 Jan 25.PubMed PMID: 18219445.

9: Gould S, Westwood FR, Curwen JO, Ashton SE, Roberts DW, Lovick SC,Ryan AJ. Effect of pretreatment with atenolol and nifedipine onZD6126-induced cardiac toxicity in rats. J Natl Cancer Inst. 2007 Nov21;99(22):1724-8. Epub 2007 Nov 13. PubMed PMID: 18000220.

10: Mocanu JD, Yip KW, Skliarenko J, Shi W, Busson P, Lo KW, BastianuttoC, Liu FF. Imaging and modulating antisense microdistribution in solidhuman xenograft tumor models. Clin Cancer Res. 2007 Oct1;13(19):5935-41. PubMed PMID: 17908990.