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+]
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
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 |
mg/mL |
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 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
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: Choi SH, Choi CH. Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs. J Audiol Otol. 2015 Dec;19(3):111-9. doi: 10.7874/jao.2015.19.3.111. Epub 2015 Dec 18. PMID: 26771008; PMCID: PMC4704551.
2: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2006 May;28(4):233-77. PMID: 16801985.
3: Bayés M, Rabasseda X, Prous JR. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jul-Aug;29(6):427-37. PMID: 17922073.
4: Ginsberg MD. Life after cerovive: a personal perspective on ischemic neuroprotection in the post-NXY-059 era. Stroke. 2007 Jun;38(6):1967-72. doi: 10.1161/STROKEAHA.106.479170. Epub 2007 May 3. PMID: 17478741.
5: Bayés M, Rabasseda X. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2008 Jan-Feb;30(1):67-99. PMID: 18389098.
6: Hallevi H, Aronowski J. Life after SAINT. Int J Stroke. 2007 Nov;2(4):241-2. doi: 10.1111/j.1747-4949.2007.00157.x. PMID: 18705923.
7: Jönsson S, Cheng YF, Edenius C, Lees KR, Odergren T, Karlsson MO. Population pharmacokinetic modelling and estimation of dosing strategy for NXY-059, a nitrone being developed for stroke. Clin Pharmacokinet. 2005;44(8):863-78. doi: 10.2165/00003088-200544080-00007. PMID: 16029070.
8: The bitterest pill. Nature. 2006 Nov 30;444(7119):532-3. doi: 10.1038/444532a. PMID: 17136064.
9: Wang CX, Shuaib A. Neuroprotective effects of free radical scavengers in stroke. Drugs Aging. 2007;24(7):537-46. doi: 10.2165/00002512-200724070-00002. PMID: 17658905.
10: Dolgin E. To serve and neuroprotect. Nat Med. 2012 Jul 6;18(7):1003-6. doi: 10.1038/nm0712-1003. PMID: 22772545.
11: Fong JJ, Rhoney DH. NXY-059: review of neuroprotective potential for acute stroke. Ann Pharmacother. 2006 Mar;40(3):461-71. doi: 10.1345/aph.1E636. Epub 2006 Feb 28. PMID: 16507608.
12: Lapchak PA. NXY-059. Centaur. Curr Opin Investig Drugs. 2002 Dec;3(12):1758-62. PMID: 12528313.
13: Ferro JM, Dávalos A. Other neuroprotective therapies on trial in acute stroke. Cerebrovasc Dis. 2006;21 Suppl 2:127-30. doi: 10.1159/000091712. Epub 2006 May 2. PMID: 16651823.
14: Lapchak PA, Song D, Wei J, Zivin JA. Coadministration of NXY-059 and tenecteplase six hours following embolic strokes in rabbits improves clinical rating scores. Exp Neurol. 2004 Aug;188(2):279-85. doi: 10.1016/j.expneurol.2004.02.005. PMID: 15246827.
15: Leker RR, Eichel R, Rafaeli G, Ben-Hur T. Novel therapies for acute ischemic stroke. Isr Med Assoc J. 2006 Nov;8(11):788-92. PMID: 17180832.
16: Minnerup J, Sutherland BA, Buchan AM, Kleinschnitz C. Neuroprotection for stroke: current status and future perspectives. Int J Mol Sci. 2012;13(9):11753-11772. doi: 10.3390/ijms130911753. Epub 2012 Sep 18. PMID: 23109881; PMCID: PMC3472773.
17: Green AR. Protecting the brain: the search for a clinically effective neuroprotective drug for stroke. Crit Rev Neurobiol. 2004;16(1-2):91-7. doi: 10.1615/critrevneurobiol.v16.i12.100. PMID: 15581404.
18: Sutherland BA, Minnerup J, Balami JS, Arba F, Buchan AM, Kleinschnitz C. Neuroprotection for ischaemic stroke: translation from the bench to the bedside. Int J Stroke. 2012 Jul;7(5):407-18. doi: 10.1111/j.1747-4949.2012.00770.x. Epub 2012 Mar 6. PMID: 22394615.
19: Green AR, Shuaib A. Therapeutic strategies for the treatment of stroke. Drug Discov Today. 2006 Aug;11(15-16):681-93. doi: 10.1016/j.drudis.2006.06.001. PMID: 16846795.
20: Villamena FA, Das A, Nash KM. Potential implication of the chemical properties and bioactivity of nitrone spin traps for therapeutics. Future Med Chem. 2012 Jun;4(9):1171-207. doi: 10.4155/fmc.12.74. PMID: 22709256; PMCID: PMC5248478.
