CAS No. : 288847-34-7

Product Details
For research use only. Not Intended for Therapeutic Use!
Cat No:I000046
Synonyms:OXi4503; OXi 4503; CA1P; tetrasodium [3-methoxy-2-phosphonatooxy-6-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate
Molecular Formula:C18H18Na4O12P2
Molecular Weight:580.23
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Cat No:I000046
Cas No:288847-34-7
OXi4503 (cas 288847-34-7, combretastatin A1-diphosphate or CA1P) is a dual-mechanism vascular disrupting agent (VDA) that is being developed for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Like its structural analog, CA4P (combretastatin A4-phosphate or fosbretabulin), OXi4503 has been observed to compromise the tumor vasculature, resulting in extensive tumor cell death and necrosis while also possibly affecting the cell shape and attachment of hematopoietic stem cells. In addition, once administered via infusion, it forms a highly reactive orthoquinone metabolite, which has been shown in preclinical studies to have antitumor activity. In preclinical studies, OXi4503 demonstrated potent activity in mice that were carriers of the high-risk subtype FLT3 of human AML.
1: Nguyen L, Fifis T, Christophi C. Vascular disruptive agent OXi4503 and anti-angiogenic agent Sunitinib combination treatment prolong survival of mice with CRC liver metastasis. BMC Cancer. 2016 Jul 26;16:533. doi: 10.1186/s12885-016-2568-7. PubMed PMID: 27460820; PubMed Central PMCID: PMC4962549.
2: Bothwell KD, Folaron M, Seshadri M. Preclinical Activity of the Vascular Disrupting Agent OXi4503 against Head and Neck Cancer. Cancers (Basel). 2016 Jan 7;8(1). pii: E11. doi: 10.3390/cancers8010011. PubMed PMID: 26751478; PubMed Central PMCID: PMC4728458.
3: Horsman MR. Therapeutic potential of using the vascular disrupting agent OXi4503 to enhance mild temperature thermoradiation. Int J Hyperthermia. 2015;31(5):453-9. doi: 10.3109/02656736.2015.1024289. Epub 2015 Apr 27. PubMed PMID: 25915829.
4: Lee JA, Biel NM, Kozikowski RT, Siemann DW, Sorg BS. In vivo spectral and fluorescence microscopy comparison of microvascular function after treatment with OXi4503, Sunitinib and their combination in Caki-2 tumors. Biomed Opt Express. 2014 May 28;5(6):1965-79. doi: 10.1364/BOE.5.001965. eCollection 2014 Jun 1. PubMed PMID: 24940553; PubMed Central PMCID: PMC4052922.
5: Fifis T, Nguyen L, Malcontenti-Wilson C, Chan LS, Nunes Costa PL, Daruwalla J, Nikfarjam M, Muralidharan V, Waltham M, Thompson EW, Christophi C. Treatment with the vascular disruptive agent OXi4503 induces an immediate and widespread epithelial to mesenchymal transition in the surviving tumor. Cancer Med. 2013 Oct;2(5):595-610. doi: 10.1002/cam4.109. Epub 2013 Aug 18. PubMed PMID: 24403226; PubMed Central PMCID: PMC3892792.
6: Stratford MR, Folkes LK. Quantitative determination of the anticancer prodrug combretastatin A1 phosphate (OXi4503, CA1P), the active CA1 and its glucuronide metabolites in human urine and of CA1 in plasma by HPLC with mass spectrometric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Jun 1;898:1-6. doi: 10.1016/j.jchromb.2012.03.040. Epub 2012 Apr 24. PubMed PMID: 22578514.
7: Cummings J, Zweifel M, Smith N, Ross P, Peters J, Rustin G, Price P, Middleton MR, Ward T, Dive C. Evaluation of cell death mechanisms induced by the vascular disrupting agent OXi4503 during a phase I clinical trial. Br J Cancer. 2012 May 22;106(11):1766-71. doi: 10.1038/bjc.2012.165. Epub 2012 Apr 26. PubMed PMID: 22538971; PubMed Central PMCID: PMC3364117.
8: Patterson DM, Zweifel M, Middleton MR, Price PM, Folkes LK, Stratford MR, Ross P, Halford S, Peters J, Balkissoon J, Chaplin DJ, Padhani AR, Rustin GJ. Phase I clinical and pharmacokinetic evaluation of the vascular-disrupting agent OXi4503 in patients with advanced solid tumors. Clin Cancer Res. 2012 Mar 1;18(5):1415-25. doi: 10.1158/1078-0432.CCR-11-2414. Epub 2012 Jan 10. PubMed PMID: 22235096.
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