Olesoxime
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| Identifiers | |
|---|---|
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| CAS Number | 22033-87-0 |
| PubChem (CID) | 21763506 |
| ChemSpider | 23350363 |
| Chemical and physical data | |
| Formula | C27H45NO |
| Molar mass | 399.65 |
| 3D model (Jmol) | Interactive image |
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Olesoxime (TRO19622) is an experimental neuroprotective drug. It is the lead compound of Trophos' cholesterol-oxime compound family of mitochondrial pore modulators.[1][2]
It is a molecule that has a cholesterol-like structure and displays neuroprotective properties. TRO19622 is as effective as a cocktail of three neurotrophic factors in keeping motor neurons alive in culture.[3]
Preclinical studies have demonstrated that the compound promotes the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP).[3]
A 2009–2011 phase 3 clinical trial of olesoxime in amyotrophic lateral sclerosis did not demonstrate a significant increase in survival versus placebo.[4]
The results of a 2011–2013 combined phase 2/3 trial of olesoxime in spinal muscular atrophy (SMA) indicated that the compound prevents deterioration of muscle function.[5]
Since 2015, olesoxime is being developed as a drug for SMA by Hoffmann-La Roche.
References
- ↑ Martin LJ (August 2010). "Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis". IDrugs. 13 (8): 568–80. PMC 3058503
. PMID 20721828. - ↑ "Olesoxime". New Drugs Online Report. UK Medicines Information.
- 1 2 Bordet T, Buisson B, Michaud M, Drouot C, Galéa P, Delaage P, Akentieva NP, Evers AS, Covey DF, Ostuni MA, Lacapère JJ, Massaad C, Schumacher M, Steidl EM, Maux D, Delaage M, Henderson CE, Pruss RM (2007). "Identification and Characterization of Cholest-4-en-3-one, Oxime (TRO19622), a Novel Drug Candidate for Amyotrophic Lateral Sclerosis". Journal of Pharmacology and Experimental Therapeutics. 322 (2): 709–720. doi:10.1124/jpet.107.123000. PMID 17496168.
- ↑ "Trophos announces results of phase 3 study of olesoxime in Amyotrophic Lateral Sclerosis". Press Release. Trophos. 2011-12-13.
- ↑ "Trophos announces top-line results of pivotal trial of olesoxime in spinal muscular atrophy". Press Release. Trophos. 2014-03-10.
Further reading
- Rovini A, Carré M, Bordet T, Pruss RM, Braguer D (2010). "Olesoxime prevents microtubule-targeting drug neurotoxicity: Selective preservation of EB comets in differentiated neuronal cells". Biochemical Pharmacology. 80 (6): 884–894. doi:10.1016/j.bcp.2010.04.018. PMID 20417191.
- Xiao WH, Zheng FY, Bennett GJ, Bordet T, Pruss RM (2009). "Olesoxime (cholest-4-en-3-one, oxime): Analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel". Pain. 147 (1–3): 202–209. doi:10.1016/j.pain.2009.09.006. PMC 2787910. PMID 19833436.
- Bordet T, Buisson B, Michaud M, Abitbol JL, Marchand F, Grist J, Andriambeloson E, Malcangio M, Pruss RM (2008). "Specific Antinociceptive Activity of Cholest-4-en-3-one, Oxime (TRO19622) in Experimental Models of Painful Diabetic and Chemotherapy-Induced Neuropathy". Journal of Pharmacology and Experimental Therapeutics. 326 (2): 623–632. doi:10.1124/jpet.108.139410. PMID 18492948.
External links
- cholest-4-en-3-one, oxime at the US National Library of Medicine Medical Subject Headings (MeSH)'