Disufenton sodium

Disufenton sodium

Clinical data
ATC code	none
Identifiers
IUPAC name Disodium 4-[(Z)-(tert-butyl-oxidoazaniumylidene)methyl]benzene-1,3-disulfonate
CAS Number	168021-79-2  Y
PubChem CID	6440181
ChemSpider	28530805  N
UNII	7M1J3HN9VO
KEGG	D03875  Y
ChEMBL	ChEMBL1627056  N
Chemical and physical data
Formula	C11H13NNa2O7S2
Molar mass	381.32 g·mol−1
3D model (JSmol)	Interactive image
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)

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]}

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

References

1. Varela-Nieto I, Murillo-Cuesta S, Rodríguez-de la Rosa L, Oset-Gasque MJ, Marco-Contelles J (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. 15 711269. Frontiers Media SA. doi: 10.3389/fncel.2021.711269 . PMC   8440819 . PMID   34539349.
2. Zhao Z, Cheng M, Maples KR, Ma JY, Buchan AM (August 2001). "NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat". Brain Research. 909 (1–2). Elsevier BV: 46–50. doi:10.1016/s0006-8993(01)02618-x. PMID   11478919. S2CID   36633423.
3. Choi SH, Choi CH (December 2015). "Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs". Journal of Audiology & Otology. 19 (3). The Korean Audiological Society: 111–119. doi:10.7874/jao.2015.19.3.111. 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): 2970–2978. doi: 10.1161/01.STR.0000249410.91473.44 . PMID   17068304.
6. "Renovis: Press Release". Archived from the original on October 28, 2006.
7. Thomas L, Smith N, Saunders D, Zalles M, Gulej R, Lerner M, et al. (November 2020). "OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma". Journal of Translational Medicine. 18 (1) 424. Springer Science and Business Media LLC. doi: 10.1186/s12967-020-02593-5 . 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 JD, Ikeguchi A, Woo S, Sharan S, Zhao YD, Cohoon A, et al. (May 20, 2020). "Phase Ib clinical trial of OKN-007 in recurrent malignant glioma". Journal of Clinical Oncology. 38 (15_suppl). American Society of Clinical Oncology (ASCO): 2538. doi:10.1200/jco.2020.38.15_suppl.2538. ISSN   0732-183X. S2CID   219772612.
10. Zalles M, Smith N, Saunders D, Lerner M, Fung KM, Battiste J, Towner RA (January 2022). "A tale of two multi-focal therapies for glioblastoma: An antibody targeting ELTD1 and nitrone-based OKN-007". Journal of Cellular and Molecular Medicine. 26 (2). Wiley: 570–582. doi:10.1111/jcmm.17133. PMC   8743651 . PMID   34910361.
11. Lu J, West MB, Du X, Cai Q, Ewert DL, Cheng W, et al. (January 7, 2021). Biagini G (ed.). "Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus". PLOS ONE. 16 (1). Public Library of Science (PLoS)\: e0243903. Bibcode:2021PLoSO..1643903L. doi: 10.1371/journal.pone.0243903 . PMC   7790300 . PMID   33411811.
12. Zhang J (November 2019). "Blast-induced tinnitus: Animal models". The Journal of the Acoustical Society of America. 146 (5). Acoustical Society of America (ASA): 3811–3831. Bibcode:2019ASAJ..146.3811Z. doi: 10.1121/1.5132551 . PMID   31795642. S2CID   208621727.
13. "Congressionally Directed Medical Research Programs (CDMRP) Search Awards". Congressionally Directed Medical Research Programs. Archived from the original on February 5, 2022. Retrieved February 5, 2022.
14. Martin B (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". The Annals of Pharmacotherapy. 40 (3): 461–471. doi:10.1345/aph.1E636. PMID   16507608. S2CID   38016035.
• Warner DS, Sheng H, Batinić-Haberle I (August 2004). "Oxidants, antioxidants and the ischemic brain". The Journal of Experimental Biology. 207 (Pt 18): 3221–3231. Bibcode:2004JExpB.207.3221W. doi:10.1242/jeb.01022. PMID   15299043. S2CID   15392635.