Disufenton sodium explained

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". 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]

Further reading

Notes and References

  1. Varela-Nieto I, Murillo-Cuesta S, Rodríguez-de la Rosa L, Oset-Gasque MJ, Marco-Contelles J . 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 . September 1, 2021 . 34539349 . 8440819 . 10.3389/fncel.2021.711269 . Frontiers Media SA . free .
  2. Zhao Z, Cheng M, Maples KR, Ma JY, Buchan AM . NXY-059, a novel free radical trapping compound, reduces cortical infarction after permanent focal cerebral ischemia in the rat . Brain Research . 909 . 1–2 . 46–50 . August 2001 . 11478919 . 10.1016/s0006-8993(01)02618-x . Elsevier BV . 36633423 .
  3. Choi SH, Choi CH . Noise-Induced Neural Degeneration and Therapeutic Effect of Antioxidant Drugs . Journal of Audiology & Otology . 19 . 3 . 111–119 . December 2015 . 26771008 . 4704551 . 10.7874/jao.2015.19.3.111 . The Korean Audiological Society .
  4. Lees KR, Zivin JA, Ashwood T, Davalos A, Davis SM, Diener HC, Grotta J, Lyden P, Shuaib A, Hårdemark HG, Wasiewski WW . 6 . NXY-059 for acute ischemic stroke . The New England Journal of Medicine . 354 . 6 . 588–600 . February 2006 . 16467546 . 10.1056/NEJMoa052980 . free .
  5. Lees KR, Davalos A, Davis SM, Diener HC, Grotta J, Lyden P, Shuaib A, Ashwood T, Hardemark HG, Wasiewski W, Emeribe U, Zivin JA . 6 . Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial . Stroke . 37 . 12 . 2970–2978 . December 2006 . 17068304 . 10.1161/01.STR.0000249410.91473.44 . free .
  6. Web site: Renovis: Press Release. https://web.archive.org/web/20061028094321/http://investors.renovis.com/phoenix.zhtml?c=148297&p=irol-newsArticle&t=Regular&id=921678& . October 28, 2006 .
  7. Thomas L, Smith N, Saunders D, Zalles M, Gulej R, Lerner M, Fung KM, Carcaboso AM, Towner RA . 6 . OKlahoma Nitrone-007: novel treatment for diffuse intrinsic pontine glioma . Journal of Translational Medicine . 18 . 1 . 424 . November 2020 . 33168005 . 7654606 . 10.1186/s12967-020-02593-5 . Springer Science and Business Media LLC . free .
  8. Web site: FDA grants fast track status to OKN-007 for diffuse intrinsic pontine glioma . Healio . March 3, 2021 . February 5, 2022.
  9. Battiste JD, Ikeguchi A, Woo S, Sharan S, Zhao YD, Cohoon A, Sung S, Wright D, Teague AM, Jensen RL, Kim EH, Yang WS, Towner RA . 6 . Phase Ib clinical trial of OKN-007 in recurrent malignant glioma. . Journal of Clinical Oncology . American Society of Clinical Oncology (ASCO) . 38 . 15_suppl . May 20, 2020 . 0732-183X . 10.1200/jco.2020.38.15_suppl.2538 . 2538. 219772612 .
  10. Zalles M, Smith N, Saunders D, Lerner M, Fung KM, Battiste J, Towner RA . 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 . 570–582 . January 2022 . 34910361 . 8743651 . 10.1111/jcmm.17133 . Wiley .
  11. Lu J, West MB, Du X, Cai Q, Ewert DL, Cheng W, Nakmali D, Li W, Huang X, Kopke RD . 6 . Electrophysiological assessment and pharmacological treatment of blast-induced tinnitus . PLOS ONE . 16 . 1 . e0243903 . January 7, 2021 . 33411811 . 7790300 . 10.1371/journal.pone.0243903 . Public Library of Science (PLoS)\. free . 2021PLoSO..1643903L . Biagini G .
  12. Zhang J . Blast-induced tinnitus: Animal models . The Journal of the Acoustical Society of America . 146 . 5 . 3811–3831 . November 2019 . 31795642 . 10.1121/1.5132551 . Acoustical Society of America (ASA) . 208621727 . free . 2019ASAJ..146.3811Z .
  13. Web site: Congressionally Directed Medical Research Programs (CDMRP) Search Awards . Congressionally Directed Medical Research Programs . February 5, 2022.
  14. Web site: Martin B . Hough Ear Institute receives $300K grant to support research treatments for hearing loss . KOKH . July 27, 2020 . February 5, 2022.

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