Disufenton sodium

Disufenton sodium (Cerovive, OKN-007, NXY-059, HPN-07)[1] is a free radical trapping nitrone-based antioxidant compound that has been under development for several medical conditions.[2][3]

Disufenton sodium
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • Disodium 4-[(Z)-(tert-butyl-oxidoazaniumylidene)methyl]benzene-1,3-disulfonate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC11H13NNa2O7S2
Molar mass381.32 g·mol−1
3D model (JSmol)
SMILES
  • CC(C)(C)[N+]([O-])=Cc1ccc(cc1S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+]
InChI
  • 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 N
  • Key:XLZOVRYBVCMCGL-UHFFFAOYSA-L N
 NY (what is this?)  (verify)

Chemistry

Disufenton sodium is the disulfonyl derivative of the neuroprotective nitrone spin trap phenylbutylnitrone or "PBN". PBN and its derivatives hydrolyze and oxidize in vitro to form respectively MNP-OH (AKA, NtBHA) and its parent spin-trap MNP.

Research

Disufenton sodium was under development at the drug company AstraZeneca. A 2005 phase-3 clinical trial[4][5] called "SAINT-1" reported some efficacy in the acute treatment of ischemia injury due to stroke. However, a 2006 attempt to repeat this trial indicated no significant activity. After ruling out other causes, the authors tentatively attributed the positive results in the first trial to "chance".[4] AstraZeneca then terminated the development programme.[6]

Disufenton sodium has been researched as a potential treatment for use in brain tumors and cancers, including diffuse intrinsic pontine glioma (DIPG)[7][8] and glioblastoma.[9][10]

A compound containing a combination of disufenton sodium and acetylcysteine (NHPN-1010) has been researched as a potential treatment for tinnitus and hearing loss.[11][12][13][14]

References
  1. Varela-Nieto, Isabel; Murillo-Cuesta, Silvia; Rodríguez-de la Rosa, Lourdes; Oset-Gasque, María Jesús; Marco-Contelles, José (September 1, 2021). "Use of Radical Oxygen Species Scavenger Nitrones to Treat Oxidative Stress-Mediated Hearing Loss: State of the Art and Challenges". Frontiers in Cellular Neuroscience. Frontiers Media SA. 15: 711269. doi:10.3389/fncel.2021.711269. ISSN 1662-5102. PMC 8440819. PMID 34539349.
  2. Zhao, Zonghang; Cheng, Mingshan; Maples, Kirk R.; Ma, Jing Ying; Buchan, Alastair M. (2001). "NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat". Brain Research. Elsevier BV. 909 (1–2): 46–50. doi:10.1016/s0006-8993(01)02618-x. ISSN 0006-8993. PMID 11478919. S2CID 36633423.
  3. Choi, Seong Hee; Choi, Chul-Hee (December 20, 2015). "Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs". Journal of Audiology and Otology. The Korean Audiological Society. 19 (3): 111–119. doi:10.7874/jao.2015.19.3.111. ISSN 2384-1621. PMC 4704551. PMID 26771008.
  4. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener HC, et al. (February 2006). "NXY-059 for acute ischemic stroke". The New England Journal of Medicine. 354 (6): 588–600. doi:10.1056/NEJMoa052980. PMID 16467546.
  5. Lees KR, Davalos A, Davis SM, Diener HC, Grotta J, Lyden P, et al. (December 2006). "Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial". Stroke. 37 (12): 2970–8. doi:10.1161/01.STR.0000249410.91473.44. PMID 17068304.
  6. "Renovis: Press Release". Archived from the original on October 28, 2006.
  7. Thomas, Lincy; Smith, Nataliya; Saunders, Debra; Zalles, Michelle; Gulej, Rafal; Lerner, Megan; Fung, Kar-Ming; Carcaboso, Angel M.; Towner, Rheal A. (November 10, 2020). "OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma". Journal of Translational Medicine. Springer Science and Business Media LLC. 18 (1): 424. doi:10.1186/s12967-020-02593-5. ISSN 1479-5876. PMC 7654606. PMID 33168005.
  8. "FDA grants fast track status to OKN-007 for diffuse intrinsic pontine glioma". Healio. March 3, 2021. Retrieved February 5, 2022.
  9. Battiste, James D.; Ikeguchi, Alexandra; Woo, Sukyung; Sharan, Satish; Zhao, Yan D.; Cohoon, Andrew; Sung, Sarah; Wright, Deborah; Teague, April M.; Jensen, Randy L.; Kim, Eun Ha; Yang, Won S.; Towner, Rheal A. (May 20, 2020). "Phase Ib clinical trial of OKN-007 in recurrent malignant glioma". Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO). 38 (15_suppl): 2538. doi:10.1200/jco.2020.38.15_suppl.2538. ISSN 0732-183X. S2CID 219772612.
  10. Zalles, Michelle; Smith, Nataliya; Saunders, Debra; Lerner, Megan; Fung, Kar‐Ming; Battiste, James; Towner, Rheal A. (December 14, 2021). "A tale of two multi‐focal therapies for glioblastoma: An antibody targeting ELTD1 and nitrone‐based OKN‐007". Journal of Cellular and Molecular Medicine. Wiley. 26 (2): 570–582. doi:10.1111/jcmm.17133. ISSN 1582-1838. PMC 8743651. PMID 34910361.
  11. Lu, Jianzhong; West, Matthew B.; Du, Xiaoping; Cai, Qunfeng; Ewert, Donald L.; Cheng, Weihua; Nakmali, Don; Li, Wei; Huang, Xiangping; Kopke, Richard D. (January 7, 2021). Biagini, Giuseppe (ed.). "Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus". PLOS ONE. Public Library of Science (PLoS). 16 (1): e0243903. Bibcode:2021PLoSO..1643903L. doi:10.1371/journal.pone.0243903. ISSN 1932-6203. PMC 7790300. PMID 33411811.
  12. Zhang, Jinsheng (2019). "Blast-induced tinnitus: Animal models". The Journal of the Acoustical Society of America. Acoustical Society of America (ASA). 146 (5): 3811–3831. Bibcode:2019ASAJ..146.3811Z. doi:10.1121/1.5132551. ISSN 0001-4966. PMID 31795642. S2CID 208621727.
  13. "Congressionally Directed Medical Research Programs (CDMRP) Search Awards". Congressionally Directed Medical Research Programs. Retrieved February 5, 2022.
  14. Martin, Brandon (July 27, 2020). "Hough Ear Institute receives $300K grant to support research treatments for hearing loss". KOKH. Retrieved February 5, 2022.

Further reading
  • Fong JJ, Rhoney DH (March 2006). "NXY-059: review of neuroprotective potential for acute stroke". Ann Pharmacother. 40 (3): 461–71. doi:10.1345/aph.1E636. PMID 16507608. S2CID 38016035.
  • Warner DS, Sheng H, Batinić-Haberle I (August 2004). "Oxidants, antioxidants and the ischemic brain". J Exp Biol. 207 (Pt 18): 3221–31. doi:10.1242/jeb.01022. PMID 15299043. S2CID 15392635.
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