WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H200721
CAS#: 168021-79-2 (sodium)
Description: Disufenton sodium, also known as Cerovive, OKN007, NXY-059, is a disulfonyl derivative of phenyl-tert-butyl nitrone (PBN), with potential anti-glioma activity. Although the exact mechanism(s) of action of OKN007 are still largely unknown, this agent appears to inhibit cancer cell proliferation and migration. This agent appears to inhibit the activity of sulfatase 2 (SULF2), a highly specific endoglucosamine-6-sulfatase that is overexpressed in the extracellular matrix of cancer cells and catalyzes the removal of sulfate from the 6-O-sulfate esters of heparin.
Hodoodo Cat#: H200721
Name: Disufenton sodium (Cerovive)
CAS#: 168021-79-2 (sodium)
Chemical Formula: C11H13NNa2O7S2
Exact Mass: 0.00
Molecular Weight: 381.330
Elemental Analysis: C, 34.65; H, 3.44; N, 3.67; Na, 12.06; O, 29.37; S, 16.82
Related CAS #: 168021-77-0 (free base) 168021-79-2 (sodium)
Synonym: NXY059; NXY 059; NXY-059; CXY 059; CXY059; CXY-059; OKN007; OKN-007; OKN 007; ARL 16556; ARL16556; ARL-16556; CPI-22; CPI22; CPI 22; Cerovive; Disufenton sodium
IUPAC/Chemical Name: sodium (Z)-4-((tert-butyloxidoazanylidene)methyl)benzene-1,3-disulfonate
InChi Key: XLZOVRYBVCMCGL-BPNVQINPSA-L
InChi Code: InChI=1S/C11H15NO7S2.2Na/c1-11(2,3)12(13)7-8-4-5-9(20(14,15)16)6-10(8)21(17,18)19;;/h4-7H,1-3H3,(H,14,15,16)(H,17,18,19);;/q;2*+1/p-2/b12-7-;;
SMILES Code: O=S(C1=CC=C(/C=[N+](C(C)(C)C)\[O-])C(S(=O)([O-])=O)=C1)([O-])=O.[Na+].[Na+]
Appearance: 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, DMF, PBS, and EtOH
Shelf Life: >5 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
More Info:
| Biological target: | Disufenton sodium (NXY-059) is the disulfonyl derivative of the neuroprotective spin trap phenylbutynitrone (PBN) and is a very powerful scavenger of free radicals. |
| In vitro activity: | To determine the specific molecular mechanisms of the antitumor effect of OKN-007 on HCC cells, this study measured the effect of OKN-007 on the activity of two well-known oncogenic signaling pathways in HCC, including TGFB1/ SMAD2 signaling and Hedgehog/GLI1 signaling. First, luciferase expression was measured in SULF2-positive Huh7 cells transfected with luciferase reporter constructs responsive to activated TGFB1 pathway SMAD transcription factors or to the Hh pathway GLI transcription factors. OKN-007 treatment significantly suppressed SMAD-responsive luciferase activity (Fig. 4A; P = 0.03), as well as GLI-responsive luciferase activity (Fig. 4B; P = 0.03). Immunoblotting confirmed the concomitant suppression of the activated transcription factors pSMAD2 (Fig. 4A) and GLI1 (Fig. 4B). These data support the hypothesis that OKN-007 treatment suppresses the activation of signaling pathways and mediators that we have previously shown to be responsive to SULF2 expression, including TGFB1/SMAD2 and Hedgehog/GLI1. Reference: Genes Chromosomes Cancer. 2013 Mar;52(3):225-36. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889201/ |
| In vivo activity: | Remarkably, this study observed that OHC (outer hair cell) loss was not only significantly reduced in HPN-07 (Disufenton sodium) treated animals in tonotopic regions corresponding to the initial insult, but its subsequent apical migration was also blocked in the treated animals.In contrast to OHC loss, which plateaued at about 10d post-insult, IHC (inner hair cell) loss continued longitudinally, with most of the loss occurring between 21 and 180d in the untreated animals. In contrast, less than 1% IHC loss was observed at all tonotopic positions in HPN-07-treated animals during the 180d study period. The progressive IHC loss observed in untreated, noise-exposed chinchilla may be attributable to ongoing inflammation or oxidative stress post-injury, both of which have been shown to be attenuated by HPN-07 treatment in other tissue injuries. The observed protection of afferent nerve fibers in the treatment group may, thus, be an indirect effect of HC protection or a direct antioxidant effect on the nerve fibers themselves. Reference: PLoS One. 2017; 12(8): e0183089. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568441/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 44.7 | 117.25 | |
| DMF | 20.0 | 52.45 | |
| Ethanol | 2.0 | 5.24 | |
| PBS (pH 7.2) | 10.0 | 26.22 | |
| Water | 54.7 | 143.47 |
The following data is based on the product molecular weight 381.33 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.
| 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 |
| Formulation protocol: | 1. Zheng X, Gai X, Han S, Moser CD, Hu C, Shire AM, Floyd RA, Roberts LR. The human sulfatase 2 inhibitor 2,4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1/SMAD2 and Hedgehog/GLI1 signaling. Genes Chromosomes Cancer. 2013 Mar;52(3):225-36. doi: 10.1002/gcc.22022. Epub 2012 Oct 29. PMID: 23109092; PMCID: PMC3889201. 2. Mutch NJ, Moore NR, Mattsson C, Jonasson H, Green AR, Booth NA. The use of the Chandler loop to examine the interaction potential of NXY-059 on the thrombolytic properties of rtPA on human thrombi in vitro. Br J Pharmacol. 2008 Jan;153(1):124-31. doi: 10.1038/sj.bjp.0707543. Epub 2007 Nov 5. PMID: 17982476; PMCID: PMC2199381. 3. Ewert D, Hu N, Du X, Li W, West MB, Choi CH, Floyd R, Kopke RD. HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma. PLoS One. 2017 Aug 23;12(8):e0183089. doi: 10.1371/journal.pone.0183089. PMID: 28832600; PMCID: PMC5568441. 4. Floyd RA, Chandru HK, He T, Towner R. Anti-cancer activity of nitrones and observations on mechanism of action. Anticancer Agents Med Chem. 2011 May 1;11(4):373-9. doi: 10.2174/187152011795677517. PMID: 21651461; PMCID: PMC3246679. |
| In vitro protocol: | 1. Zheng X, Gai X, Han S, Moser CD, Hu C, Shire AM, Floyd RA, Roberts LR. The human sulfatase 2 inhibitor 2,4-disulfonylphenyl-tert-butylnitrone (OKN-007) has an antitumor effect in hepatocellular carcinoma mediated via suppression of TGFB1/SMAD2 and Hedgehog/GLI1 signaling. Genes Chromosomes Cancer. 2013 Mar;52(3):225-36. doi: 10.1002/gcc.22022. Epub 2012 Oct 29. PMID: 23109092; PMCID: PMC3889201. 2. Mutch NJ, Moore NR, Mattsson C, Jonasson H, Green AR, Booth NA. The use of the Chandler loop to examine the interaction potential of NXY-059 on the thrombolytic properties of rtPA on human thrombi in vitro. Br J Pharmacol. 2008 Jan;153(1):124-31. doi: 10.1038/sj.bjp.0707543. Epub 2007 Nov 5. PMID: 17982476; PMCID: PMC2199381. |
| In vivo protocol: | 1. Ewert D, Hu N, Du X, Li W, West MB, Choi CH, Floyd R, Kopke RD. HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma. PLoS One. 2017 Aug 23;12(8):e0183089. doi: 10.1371/journal.pone.0183089. PMID: 28832600; PMCID: PMC5568441. 2. Floyd RA, Chandru HK, He T, Towner R. Anti-cancer activity of nitrones and observations on mechanism of action. Anticancer Agents Med Chem. 2011 May 1;11(4):373-9. doi: 10.2174/187152011795677517. PMID: 21651461; PMCID: PMC3246679. |
1: Lapchak PA, McKim JM Jr. CeeTox™ Analysis of CNB-001 a Novel Curcumin-Based Neurotrophic/Neuroprotective Lead Compound to Treat Stroke: Comparison with NXY-059 and Radicut. Transl Stroke Res. 2011 Mar;2(1):51-59. PubMed PMID: 21494575; PubMed Central PMCID: PMC3074116.
2: Culot M, Mysiorek C, Renftel M, Roussel BD, Hommet Y, Vivien D, Cecchelli R, Fenart L, Berezowski V, Dehouck MP, Lundquist S. Cerebrovascular protection as a possible mechanism for the protective effects of NXY-059 in preclinical models: an in vitro study. Brain Res. 2009 Oct 19;1294:144-52. doi: 10.1016/j.brainres.2009.07.035. Epub 2009 Jul 23. PubMed PMID: 19631615.
3: Bath PM, Gray LJ, Bath AJ, Buchan A, Miyata T, Green AR; NXY-059 Efficacy Meta-analysis in Individual Animals with Stroke Investigators. Effects of NXY-059 in experimental stroke: an individual animal meta-analysis. Br J Pharmacol. 2009 Aug;157(7):1157-71. doi: 10.1111/j.1476-5381.2009.00196.x. Epub 2009 Apr 27. PubMed PMID: 19422398; PubMed Central PMCID: PMC2743834.
4: Cheng YF, Jiang J, Hu P, Reinholdsson I, Guo W, Asenblad N, Nilsson D. Pharmacokinetics of 8-hour intravenous infusion of NXY-059: a phase I, randomized, double-blind (within dose panels), placebo-controlled study in healthy Chinese volunteers. Clin Ther. 2008 Dec;30(12):2342-53. doi: 10.1016/j.clinthera.2008.12.013. PubMed PMID: 19167593.
5: Clausen F, Marklund N, Lewén A, Hillered L. The nitrone free radical scavenger NXY-059 is neuroprotective when administered after traumatic brain injury in the rat. J Neurotrauma. 2008 Dec;25(12):1449-57. doi: 10.1089/neu.2008.0585. PubMed PMID: 19118455.
6: Savitz SI. Cosmic implications of NXY-059. Stroke. 2009 Mar;40(3 Suppl):S115-8. doi: 10.1161/STROKEAHA.108.535112. Epub 2008 Dec 8. PubMed PMID: 19064771.
7: Macleod MR, van der Worp HB, Sena ES, Howells DW, Dirnagl U, Donnan GA. Evidence for the efficacy of NXY-059 in experimental focal cerebral ischaemia is confounded by study quality. Stroke. 2008 Oct;39(10):2824-9. doi: 10.1161/STROKEAHA.108.515957. Epub 2008 Jul 17. PubMed PMID: 18635842.
8: Diener HC, Lees KR, Lyden P, Grotta J, Davalos A, Davis SM, Shuaib A, Ashwood T, Wasiewski W, Alderfer V, HÃ¥rdemark HG, Rodichok L; SAINT I and II Investigators. NXY-059 for the treatment of acute stroke: pooled analysis of the SAINT I and II Trials. Stroke. 2008 Jun;39(6):1751-8. doi: 10.1161/STROKEAHA.107.503334. Epub 2008 Mar 27. PubMed PMID: 18369171.
9: Savitz SI, Fisher M. NXY-059 for the treatment of stroke. N Engl J Med. 2007 Nov 22;357(21):2198; author reply 2198-9. PubMed PMID: 18032772.
10: Mutch NJ, Moore NR, Mattsson C, Jonasson H, Green AR, Booth NA. The use of the Chandler loop to examine the interaction potential of NXY-059 on the thrombolytic properties of rtPA on human thrombi in vitro. Br J Pharmacol. 2008 Jan;153(1):124-31. Epub 2007 Nov 5. PubMed PMID: 17982476; PubMed Central PMCID: PMC2199381.
