Disufenton sodium
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Formula | C11H13NNa2O7S2 |
Molar mass | 381.32 g·mol−1 |
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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]
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]
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.
References
- ↑ 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. doi:10.3389/fncel.2021.711269. ISSN 1662-5102.
- ↑ 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.
- ↑ 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.
- 1 2 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.
- ↑ 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.
- ↑ "Renovis: Press Release". Archived from the original on October 28, 2006.
- ↑ 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). doi:10.1186/s12967-020-02593-5. ISSN 1479-5876.
- ↑ "FDA grants fast track status to OKN-007 for diffuse intrinsic pontine glioma". Healio. March 3, 2021. Retrieved February 5, 2022.
- ↑ 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): 2538–2538. doi:10.1200/jco.2020.38.15_suppl.2538. ISSN 0732-183X.
- ↑ 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.
- ↑ 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. doi:10.1371/journal.pone.0243903. ISSN 1932-6203.
- ↑ 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. doi:10.1121/1.5132551. ISSN 0001-4966.
- ↑ "Congressionally Directed Medical Research Programs (CDMRP) Search Awards". Congressionally Directed Medical Research Programs. Retrieved February 5, 2022.
- ↑ Martin, Brandon (July 27, 2020). "Hough Ear Institute receives $300K grant to support research treatments for hearing loss". KOKH. Retrieved February 5, 2022.