Vadimezan (DMXAA)

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

Description:Vadimezan, also known as DMXAA and ASA404, is a fused tricyclic analogue of flavone acetic acid with potential antineoplastic activity. Vadimezan induces the cytokines tumor necrosis alpha (TNF-alpha), serotonin and nitric oxide, resulting in hemorrhagic necrosis and a decrease in angiogenesis. This agent also stimulates the anti-tumor activity of tumor-associated macrophages.

Price and Availability

Vadimezan, purity > 98%, is in stock. The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 201050Name: Vadimezan (DMXAA)CAS#: 117570-53-3Chemical Formula: C17H14O4Exact Mass: 282.08921Molecular Weight: 282.29Elemental Analysis:C, 72.33; H, 5.00; O, 22.67.

Synonym:ASA404; ASA 404; ASA404; AS1404; AS 1404; AS1404; DMXAA; Vadimezan

IUPAC/Chemical Name:(5,6-Dimethyl-9-oxo-9H-xanthen-4-yl)-acetic acid

InChi Key:XGOYIMQSIKSOBS-UHFFFAOYSA-N

InChi Code:InChI=1S/C17H14O4/c1-9-6-7-13-15(20)12-5-3-4-11(8-14(18)19)17(12)21-16(13)10(9)2/h3-7H,8H2,1-2H3,(H,18,19)

SMILES Code:O=C(O)CC1=CC=CC(C2=O)=C1OC3=C2C=CC(C)=C3C

Technical Data

Additional Information

Vadimezan or ASA404 (originally DMXAA) is a tumor-vascular disrupting agent (tumor-VDA) that attacks the blood supply of a cancerous tumor to cause tumor regression.  ASA404 was discovered by Bruce Baguley and William Denny and their teams at the Auckland Cancer Society Research Centre at the University of Auckland in New Zealand.[6] It was licensed to Antisoma in 2001. Novartis acquired the worldwide rights for it in 2007 and it is being developed by Antisoma and Novartis. See wikipedia. Novartis announced today (November 11, 2010) that the clinical trial program for the investigational cancer treatment ASA404 (vadimezan) will be discontinued and resources will be reallocated to other compounds in the oncology pipeline. The decision was made after interim results from a Phase III trial showed that ASA404 would not likely meet the primary endpoint of significantly extending overall survival when used in combination with chemotherapy for the second-line treatment of patients with advanced non-small cell lung cancer (NSCLC). (source: http://www.novartis.com/newsroom/media-releases/en/2010/1461276.shtml).(source: http://www.novartis.com/newsroom/media-releases/en/2010/1461276.shtml).   

References

1: Lou YC, Kao YF, Chin KH, Chen JK, Tu JL, Chen C,Chou SH. Backbone resonance assignments of the 54 kDa dimeric C-terminaldomain of murine STING in complex with DMXAA. Biomol NMR Assign. 2014Dec 9. [Epub ahead of print] PubMed PMID: 25487675.

2: Gao P, Zillinger T, Wang W, Ascano M, Dai P, Hartmann G, Tuschl T,Deng L, Barchet W, Patel DJ. Binding-pocket and lid-region substitutionsrender human STING sensitive to the species-specific drug DMXAA. CellRep. 2014 Sep 25;8(6):1668-76. doi: 10.1016/j.celrep.2014.08.010. Epub2014 Sep 4. PubMed PMID: 25199835.

3: Downey CM, Aghaei M, Schwendener RA, Jirik FR. DMXAA causes tumorsite-specific vascular disruption in murine non-small cell lung cancer,and like the endogenous non-canonical cyclic dinucleotide STING agonist,2"3"-cGAMP, induces M2 macrophage repolarization. PLoS One. 2014 Jun18;9(6):e99988. doi: 10.1371/journal.pone.0099988. eCollection 2014.PubMed PMID: 24940883; PubMed Central PMCID: PMC4062468.

4: Yung R, Seyfoddin V, Guise C, Tijono S, McGregor A, Connor B, ChingLM. Efficacy against subcutaneous or intracranial murine GL261 gliomasin relation to the concentration of the vascular-disrupting agent,5,6-dimethylxanthenone-4-acetic acid (DMXAA), in the brain and plasma.Cancer Chemother Pharmacol. 2014 Mar;73(3):639-49. doi:10.1007/s00280-014-2395-y. Epub 2014 Jan 30. PubMed PMID: 24477604.

5: Gao P, Ascano M, Zillinger T, Wang W, Dai P, Serganov AA, Gaffney BL,Shuman S, Jones RA, Deng L, Hartmann G, Barchet W, Tuschl T, Patel DJ.Structure-function analysis of STING activation by c[G(2",5")pA(3",5")p]and targeting by antiviral DMXAA. Cell. 2013 Aug 15;154(4):748-62. doi:10.1016/j.cell.2013.07.023. Epub 2013 Aug 1. PubMed PMID: 23910378.

6: Tang CK, Aoshi T, Jounai N, Ito J, Ohata K, Kobiyama K, Dessailly BH,Kuroda E, Akira S, Mizuguchi K, Coban C, Ishii KJ. The chemotherapeuticagent DMXAA as a unique IRF3-dependent type-2 vaccine adjuvant. PLoSOne. 2013;8(3):e60038. doi: 10.1371/journal.pone.0060038. Epub 2013 Mar21. PubMed PMID: 23555875; PubMed Central PMCID: PMC3605442.

7: Tijono SM, Guo K, Henare K, Palmer BD, Wang LC, Albelda SM, Ching LM.Identification of human-selective analogues of the vascular-disruptingagent 5,6-dimethylxanthenone-4-acetic acid (DMXAA). Br J Cancer. 2013Apr 2;108(6):1306-15. doi: 10.1038/bjc.2013.101. Epub 2013 Mar 12.PubMed PMID: 23481185; PubMed Central PMCID: PMC3619269.

8: Yeniceli D, Deng X, Adams E, Dogrukol-Ak D, Van Schepdael A.Development of a CD-MEKC method for investigating the metabolism oftamoxifen by flavin-containing monooxygenases and the inhibitory effectsof methimazole, nicotine and DMXAA. Electrophoresis. 2013Feb;34(3):463-70. doi: 10.1002/elps.201200356. Epub 2012 Dec 26. PubMedPMID: 23161341.

9: Prantner D, Perkins DJ, Lai W, Williams MS, Sharma S, Fitzgerald KA,Vogel SN. 5,6-Dimethylxanthenone-4-acetic acid (DMXAA) activatesstimulator of interferon gene (STING)-dependent innate immune pathwaysand is regulated by mitochondrial membrane potential. J Biol Chem. 2012Nov 16;287(47):39776-88. doi: 10.1074/jbc.M112.382986. Epub 2012 Oct 1.PubMed PMID: 23027866; PubMed Central PMCID: PMC3501038.

10: Henare K, Wang L, Wang LC, Thomsen L, Tijono S, Chen CJ, Winkler S,Dunbar PR, Print C, Ching LM. Dissection of stromal and cancercell-derived signals in melanoma xenografts before and after treatmentwith DMXAA. Br J Cancer. 2012 Mar 13;106(6):1134-47. doi:10.1038/bjc.2012.63. PubMed PMID: 22415295; PubMed Central PMCID:PMC3304430.

11: McKeage MJ, Jameson MB; AS1404-201 Study Group Investigators.Comparative outcomes of squamous and non-squamous non-small cell lungcancer (NSCLC) patients in phase II studies of ASA404 (DMXAA) -retrospective analysis of pooled data. J Thorac Dis. 2010Dec;2(4):199-204. doi: 10.3978/j.issn.2072-1439.2010.02.04.1. PubMedPMID: 22263047; PubMed Central PMCID: PMC3256477.

12: Buchanan CM, Shih JH, Astin JW, Rewcastle GW, Flanagan JU, CrosierPS, Shepherd PR. DMXAA (Vadimezan, ASA404) is a multi-kinase inhibitortargeting VEGFR2 in particular. Clin Sci (Lond). 2012 May1;122(10):449-57. doi: 10.1042/CS20110412. PubMed PMID: 22142330.

13: Jameson MB, Head M. Pharmacokinetic evaluation of vadimezan (ASA404,5,6-dimethylxanthenone-4-acetic acid, DMXAA). Expert Opin Drug MetabToxicol. 2011 Oct;7(10):1315-26. doi: 10.1517/17425255.2011.614389. Epub2011 Aug 26. Review. PubMed PMID: 21870897.

14: Marysael T, Ni Y, Lerut E, de Witte P. Influence of the vasculardamaging agents DMXAA and ZD6126 on hypericin distribution andaccumulation in RIF-1 tumors. J Cancer Res Clin Oncol. 2011Nov;137(11):1619-27. doi: 10.1007/s00432-011-1032-y. Epub 2011 Aug 21.PubMed PMID: 21858709.

15: Sun J, Wang LC, Fridlender ZG, Kapoor V, Cheng G, Ching LM, AlbeldaSM. Activation of mitogen-activated protein kinases by5,6-dimethylxanthenone-4-acetic acid (DMXAA) plays an important role inmacrophage stimulation. Biochem Pharmacol. 2011 Nov 1;82(9):1175-85. doi:10.1016/j.bcp.2011.07.086. Epub 2011 Jul 26. PubMed PMID: 21819972;PubMed Central PMCID: PMC3191304.

16: Peng S, Monie A, Pang X, Hung CF, Wu TC. Vascular disrupting agentDMXAA enhances the antitumor effects generated by therapeutic HPV DNAvaccines. J Biomed Sci. 2011 Mar 8;18:21. doi: 10.1186/1423-0127-18-21.PubMed PMID: 21385449; PubMed Central PMCID: PMC3062584.

17: Shirey KA, Nhu QM, Yim KC, Roberts ZJ, Teijaro JR, Farber DL, BlancoJC, Vogel SN. The anti-tumor agent, 5,6-dimethylxanthenone-4-acetic acid(DMXAA), induces IFN-beta-mediated antiviral activity in vitro and invivo. J Leukoc Biol. 2011 Mar;89(3):351-7. doi: 10.1189/jlb.0410216.Epub 2010 Nov 17. PubMed PMID: 21084628; PubMed Central PMCID:PMC3040469.

18: Baguley BC, Siemann DW. Temporal aspects of the action of ASA404 (vadimezan;DMXAA). Expert Opin Investig Drugs. 2010 Nov;19(11):1413-25. doi:10.1517/13543784.2010.529128. Review. PubMed PMID: 20964495; PubMedCentral PMCID: PMC3583340.

19: Brauer R, Wang LC, Woon ST, Bridewell DJ, Henare K, Malinger D,Palmer BD, Vogel SN, Kieda C, Tijono SM, Ching LM. Labeling ofoxidizable proteins with a photoactivatable analog of the antitumoragent DMXAA: evidence for redox signaling in its mode of action.Neoplasia. 2010 Sep;12(9):755-65. PubMed PMID: 20824052; PubMed CentralPMCID: PMC2933696.

20: Head M, Jameson MB. The development of the tumor vascular-disruptingagent ASA404 (vadimezan, DMXAA): current status and futureopportunities. Expert Opin Investig Drugs. 2010 Feb;19(2):295-304. doi:10.1517/13543780903540214. PubMed PMID: 20050824.