Olesoxime | TRO-19622 | CAS#22033-87-0 | neuroprotective

MedKoo Cat#: 319874 | Name: Olesoxime

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Olesoxime, also known as TRO-19622 and RG6083, is an experimental neuroprotective drug. Olesoxime has a cholesterol-like structure and displays neuroprotective properties. 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).

Chemical Structure

Olesoxime

CAS#22033-87-0

Theoretical Analysis

MedKoo Cat#: 319874

Name: Olesoxime

CAS#: 22033-87-0

Chemical Formula: C27H45NO

Exact Mass: 399.3501

Molecular Weight: 399.66

Elemental Analysis: C, 81.14; H, 11.35; N, 3.50; O, 4.00

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 350.00	2 Weeks
50mg	USD 1,150.00	2 Weeks

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Related CAS #

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Synonym

TRO-19622; TRO19622; TRO19622; RG6083; RG 6083; RG-6083; NSC 21311; NSC-21311; NSC21311; Olesoxime

IUPAC/Chemical Name

(8S,9S,10R,13R,14S,17R,E)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one oxime

InChi Key

QNTASHOAVRSLMD-SIWSWZRQSA-N

InChi Code

InChI=1S/C27H45NO/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28-29)13-15-26(20,4)25(22)14-16-27(23,24)5/h17-19,22-25,29H,6-16H2,1-5H3/b28-21+/t19-,22+,23-,24+,25+,26+,27-/m1/s1

SMILES Code

O/N=C1CC[C@]2(C)[C@@]3([H])CC[C@]4(C)[C@@H]([C@H](C)CCCC(C)C)CC[C@@]4([H])[C@]3([H])CCC2=C\1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Olesoxime, also known as TRO-19622 and RG6083, is a mitochondrial-targeted neuroprotective agent.

In vitro activity:

Electrophysiological analysis revealed that olesoxime suppressed selectively evoked neurotransmitter release in response to a single stimulus and 20 Hz activity. Also olesoxime decreased the rate of FM1-43 dye loss (an indicator of synaptic vesicle exocytosis) at low frequency stimulation and 20 Hz. Furthermore, an increase in extracellular Cl- enhanced the action of olesoxime on the exocytosis and olesoxime increased intracellular Cl- levels. Reference: Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Sep;1865(9):158739. https://pubmed.ncbi.nlm.nih.gov/32428575/

In vivo activity:

This study evaluated 14 mature Chinchilla bastard rabbits of 1,500-2,000 g. Rabbit hearts were isolated and perfused with constant pressure according to Langendorff. After induction of cardioplegic arrest (30 ml 4°C cold Custodiol cardioplegia without and with 5 μmol/L olesoxime, n = 7 each) the hearts maintained arrested for 90-min. Thereafter, the hearts were re-perfused for 60 min. Histological analysis revealed that despite the same ischemic burden for both groups markers of nitrosative and oxidative stress were significantly lower in the olesoxime group. Moreover, hearts of the olesoxime-group showed a significantly faster and better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels were significantly higher in the olesoxime treated hearts. Reference: Front Physiol. 2017 May 19;8:324. https://pubmed.ncbi.nlm.nih.gov/28579963/

	Solvent	mg/mL	mM
Solubility
	DMF	2.0	5.00
	DMSO	0.1	0.25
	Ethanol	20.0	50.04
	Ethanol:PBS (pH 7.2) (1:2)	0.3	0.75

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 399.66 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Zakyrjanova GF, Gilmutdinov AI, Tsentsevitsky AN, Petrov AM. Olesoxime, a cholesterol-like neuroprotectant restrains synaptic vesicle exocytosis in the mice motor nerve terminals: Possible role of VDACs. Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Sep;1865(9):158739. doi: 10.1016/j.bbalip.2020.158739. Epub 2020 May 16. PMID: 32428575. 2. Kaviani M, Keshtkar S, Azarpira N, Aghdaei MH, Geramizadeh B, Karimi MH, Shamsaeefar A, Motazedian N, Nikeghbalian S, Al-Abdullah IH, Ghahremani MH. Cytoprotective effects of olesoxime on isolated human pancreatic islets in order to attenuate apoptotic pathway. Biomed Pharmacother. 2019 Apr;112:108674. doi: 10.1016/j.biopha.2019.108674. Epub 2019 Feb 19. PMID: 30784942. 3. Salameh A, Keller M, Dähnert I, Dhein S. Olesoxime Inhibits Cardioplegia-Induced Ischemia/Reperfusion Injury. A Study in Langendorff-Perfused Rabbit Hearts. Front Physiol. 2017 May 19;8:324. doi: 10.3389/fphys.2017.00324. PMID: 28579963; PMCID: PMC5437207. 4. Clemens LE, Weber JJ, Wlodkowski TT, Yu-Taeger L, Michaud M, Calaminus C, Eckert SH, Gaca J, Weiss A, Magg JC, Jansson EK, Eckert GP, Pichler BJ, Bordet T, Pruss RM, Riess O, Nguyen HP. Olesoxime suppresses calpain activation and mutant huntingtin fragmentation in the BACHD rat. Brain. 2015 Dec;138(Pt 12):3632-53. doi: 10.1093/brain/awv290. Epub 2015 Oct 21. PMID: 26490331.

In vitro protocol:

In vivo protocol:

1. Salameh A, Keller M, Dähnert I, Dhein S. Olesoxime Inhibits Cardioplegia-Induced Ischemia/Reperfusion Injury. A Study in Langendorff-Perfused Rabbit Hearts. Front Physiol. 2017 May 19;8:324. doi: 10.3389/fphys.2017.00324. PMID: 28579963; PMCID: PMC5437207. 2. Clemens LE, Weber JJ, Wlodkowski TT, Yu-Taeger L, Michaud M, Calaminus C, Eckert SH, Gaca J, Weiss A, Magg JC, Jansson EK, Eckert GP, Pichler BJ, Bordet T, Pruss RM, Riess O, Nguyen HP. Olesoxime suppresses calpain activation and mutant huntingtin fragmentation in the BACHD rat. Brain. 2015 Dec;138(Pt 12):3632-53. doi: 10.1093/brain/awv290. Epub 2015 Oct 21. PMID: 26490331.

1: Clemens LE, Weber JJ, Wlodkowski TT, Yu-Taeger L, Michaud M, Calaminus C, Eckert SH, Gaca J, Weiss A, Magg JC, Jansson EK, Eckert GP, Pichler BJ, Bordet T, Pruss RM, Riess O, Nguyen HP. Olesoxime suppresses calpain activation and mutant huntingtin fragmentation in the BACHD rat. Brain. 2015 Dec;138(Pt 12):3632-53. doi: 10.1093/brain/awv290. Epub 2015 Oct 21. PubMed PMID: 26490331. 2: Rafiq MK, Lee E, Bradburn M, McDermott CJ, Shaw PJ. Effect of lipid profile on prognosis in the patients with amyotrophic lateral sclerosis: Insights from the olesoxime clinical trial. Amyotroph Lateral Scler Frontotemporal Degener. 2015 Dec;16(7-8):478-84. doi: 10.3109/21678421.2015.1062517. Epub 2015 Jul 10. PubMed PMID: 26161993. 3: Kaczmarek A, Schneider S, Wirth B, Riessland M. Investigational therapies for the treatment of spinal muscular atrophy. Expert Opin Investig Drugs. 2015;24(7):867-81. doi: 10.1517/13543784.2015.1038341. Epub 2015 Apr 24. PubMed PMID: 25911060. 4: Gouarné C, Tracz J, Paoli MG, Deluca V, Seimandi M, Tardif G, Xilouri M, Stefanis L, Bordet T, Pruss RM. Protective role of olesoxime against wild-type α-synuclein-induced toxicity in human neuronally differentiated SHSY-5Y cells. Br J Pharmacol. 2015 Jan;172(1):235-45. doi: 10.1111/bph.12939. Epub 2014 Dec 1. PubMed PMID: 25220617; PubMed Central PMCID: PMC4280980. 5: Richter F, Gao F, Medvedeva V, Lee P, Bove N, Fleming SM, Michaud M, Lemesre V, Patassini S, De La Rosa K, Mulligan CK, Sioshansi PC, Zhu C, Coppola G, Bordet T, Pruss RM, Chesselet MF. Chronic administration of cholesterol oximes in mice increases transcription of cytoprotective genes and improves transcriptome alterations induced by alpha-synuclein overexpression in nigrostriatal dopaminergic neurons. Neurobiol Dis. 2014 Sep;69:263-75. doi: 10.1016/j.nbd.2014.05.012. Epub 2014 May 18. PubMed PMID: 24844147; PubMed Central PMCID: PMC4135465. 6: Eckmann J, Clemens LE, Eckert SH, Hagl S, Yu-Taeger L, Bordet T, Pruss RM, Muller WE, Leuner K, Nguyen HP, Eckert GP. Mitochondrial membrane fluidity is consistently increased in different models of Huntington disease: restorative effects of olesoxime. Mol Neurobiol. 2014 Aug;50(1):107-18. doi: 10.1007/s12035-014-8663-3. Epub 2014 Mar 18. PubMed PMID: 24633813. 7: Lenglet T, Lacomblez L, Abitbol JL, Ludolph A, Mora JS, Robberecht W, Shaw PJ, Pruss RM, Cuvier V, Meininger V; Mitotarget study group. A phase II-III trial of olesoxime in subjects with amyotrophic lateral sclerosis. Eur J Neurol. 2014 Mar;21(3):529-36. doi: 10.1111/ene.12344. Epub 2014 Jan 21. PubMed PMID: 24447620. 8: Zanetta C, Nizzardo M, Simone C, Monguzzi E, Bresolin N, Comi GP, Corti S. Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials. Clin Ther. 2014 Jan 1;36(1):128-40. doi: 10.1016/j.clinthera.2013.11.006. Epub 2013 Dec 17. Review. PubMed PMID: 24360800. 9: Ma Q, Chen S, Hu Q, Feng H, Zhang JH, Tang J. NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage. Ann Neurol. 2014 Feb;75(2):209-19. doi: 10.1002/ana.24070. Epub 2014 Jan 2. PubMed PMID: 24273204; PubMed Central PMCID: PMC4386653. 10: Li Y, Zhang Y, Han W, Hu F, Qian Y, Chen Q. TRO19622 promotes myelin repair in a rat model of demyelination. Int J Neurosci. 2013 Nov;123(11):810-22. doi: 10.3109/00207454.2013.804523. Epub 2013 Jun 5. PubMed PMID: 23668883. 11: Yang YM, Gupta SK, Kim KJ, Powers BE, Cerqueira A, Wainger BJ, Ngo HD, Rosowski KA, Schein PA, Ackeifi CA, Arvanites AC, Davidow LS, Woolf CJ, Rubin LL. A small molecule screen in stem-cell-derived motor neurons identifies a kinase inhibitor as a candidate therapeutic for ALS. Cell Stem Cell. 2013 Jun 6;12(6):713-26. doi: 10.1016/j.stem.2013.04.003. Epub 2013 Apr 18. PubMed PMID: 23602540; PubMed Central PMCID: PMC3707511. 12: Gouarné C, Giraudon-Paoli M, Seimandi M, Biscarrat C, Tardif G, Pruss RM, Bordet T. Olesoxime protects embryonic cortical neurons from camptothecin intoxication by a mechanism distinct from BDNF. Br J Pharmacol. 2013 Apr;168(8):1975-88. doi: 10.1111/bph.12094. PubMed PMID: 23278424; PubMed Central PMCID: PMC3623066. 13: Ghanizadeh A. Targeting Mitochondria by Olesoxime or Complement 1q Binding Protein as a Novel Management for Autism: A Hypothesis. Mol Syndromol. 2011 Dec;2(1):50-52. Epub 2011 Oct 12. PubMed PMID: 22570645; PubMed Central PMCID: PMC3343746. 14: Sunyach C, Michaud M, Arnoux T, Bernard-Marissal N, Aebischer J, Latyszenok V, Gouarné C, Raoul C, Pruss RM, Bordet T, Pettmann B. Olesoxime delays muscle denervation, astrogliosis, microglial activation and motoneuron death in an ALS mouse model. Neuropharmacology. 2012 Jun;62(7):2346-52. doi: 10.1016/j.neuropharm.2012.02.013. Epub 2012 Feb 20. PubMed PMID: 22369784. 15: Magalon K, Zimmer C, Cayre M, Khaldi J, Bourbon C, Robles I, Tardif G, Viola A, Pruss RM, Bordet T, Durbec P. Olesoxime accelerates myelination and promotes repair in models of demyelination. Ann Neurol. 2012 Feb;71(2):213-26. doi: 10.1002/ana.22593. PubMed PMID: 22367994. 16: Xiao WH, Zheng H, Bennett GJ. Characterization of oxaliplatin-induced chronic painful peripheral neuropathy in the rat and comparison with the neuropathy induced by paclitaxel. Neuroscience. 2012 Feb 17;203:194-206. doi: 10.1016/j.neuroscience.2011.12.023. Epub 2011 Dec 20. PubMed PMID: 22200546; PubMed Central PMCID: PMC3273641. 17: Martin LJ, Adams NA, Pan Y, Price A, Wong M. The mitochondrial permeability transition pore regulates nitric oxide-mediated apoptosis of neurons induced by target deprivation. J Neurosci. 2011 Jan 5;31(1):359-70. doi: 10.1523/JNEUROSCI.2225-10.2011. PubMed PMID: 21209222; PubMed Central PMCID: PMC3078575. 18: Martin LJ. Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Aug;13(8):568-80. Review. PubMed PMID: 20721828; PubMed Central PMCID: PMC3058503. 19: Rovini A, Carré M, Bordet T, Pruss RM, Braguer D. Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells. Biochem Pharmacol. 2010 Sep 15;80(6):884-94. doi: 10.1016/j.bcp.2010.04.018. Epub 2010 Apr 22. PubMed PMID: 20417191. 20: Kirk R. Clinical trials in CNS--SMi's eighth annual conference. IDrugs. 2010 Feb;13(2):66-9. PubMed PMID: 20127552.