| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: =99.62%
Olesoxime (E/Z-olesoxime; formerly known as TRO 19622; RG-6083) is a mitochondrial-targeted neuroprotective agent with EC50 value for increasing cell survival is 3.2±0.2 µM. Olesoxime, with a cholesterol-like structure, displays neuroprotective properties in preclinical studies, it has been 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).
| Targets |
Mitochondrial; neuroprotective
|
|---|---|
| ln Vitro |
After being treated without neurotrophic factors derived from the brain, ciliary body, or glia, primary embryonic rat spinal MN were significantly protected against cell damage and death by exposure to Olesoxime (TRO 19622) at concentrations ranging from 0.1 to 10 µM one hour after inoculation. This protection persisted for three days in culture. Olesoxime (TRO 19622), at a concentration of 10 µM, sustains 74±10% neuronal survival by the action of a mixture of neurotrophic factors, including those produced from the brain, ciliary bodies, and glial cells. In this test, the average EC50 was 3.2±0.2 µM. Olesoxime (TRO 19622) not only shields MN cell bodies but also encourages neurite development. At a 1 µM concentration, olesoxime (TRO 19622) only slightly improved cell viability but significantly boosted neurite development per cell by 54% [1]. A novel class of cholesterol oximes known as olesoxime (TRO 19622) was discovered due to its ability to increase the survival of pure motor neurons in the absence of neurotrophic factors. Olesoxime (TRO 19622) selectively targets proteins in the outer membrane of the mitochondria, focusing on the mitochondria and inhibiting oxidative stress-mediated permeability transition pore opening, among other processes[2].
|
| ln Vivo |
Adult mice receiving daily subcutaneous injections of Olesoxime (TRO 19622) (3 or 30 mg/kg) for more than two months was well tolerated without toxicity or adverse effects [1]. Olesoxime (TRO 19622) increased motor neuron cell body survival in a dose-dependent manner when animals were treated orally for five days post-lesion; at this dose, motor neuron survival was 29 ±2% (n=18), a 42% increase in survival compared to vehicle-treated animals [3]. Paclitaxel-treated rats receiving prophylactic treatment with 3 mg/kg/d or 30 mg/kg/d Olesoxime (TRO 19622) had 239±17.6 and 247±14.4 IENF/cm, respectively. For both doses, the decrease was significantly smaller than the 46% seen in vehicle-administered paclitaxel-treated rats.
|
| Enzyme Assay |
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive death of cortical and spinal motor neurons, for which there is no effective treatment. Using a cell-based assay for compounds capable of preventing motor neuron cell death in vitro, a collection of approximately 40,000 low-molecular-weight compounds was screened to identify potential small-molecule therapeutics. We report the identification of cholest-4-en-3-one, oxime (TRO19622) as a potential drug candidate for the treatment of ALS. In vitro, TRO19622 promoted motor neuron survival in the absence of trophic support in a dose-dependent manner[3].
|
| Animal Protocol |
In vivo, TRO19622 rescued motor neurons from axotomy-induced cell death in neonatal rats and promoted nerve regeneration following sciatic nerve crush in mice. In SOD1G93A transgenic mice, a model of familial ALS, TRO19622 treatment improved motor performance, delayed the onset of the clinical disease, and extended survival. TRO19622 bound directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel and the translocator protein 18 kDa (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity. TRO19622 may have therapeutic potential for ALS and other motor neuron and neurodegenerative diseases[3].
|
| References |
|
| Additional Infomation |
Olesoxime is a cholesterol-like small molecule that has demonstrated a remarkable neuroprotective profile in a battery of both in vitro and in vivo preclinical models. For example, it has demonstrated the ability to prevent neurodegeneration, enhance nerve function and accelerate neuroregeneration following nerve trauma.
Drug Indication Investigated for use/treatment in neurologic disorders. Treatment of spinal muscular atrophy Mechanism of Action Olesoxime interacts with a physiologically relevant target: the mitochondrial permeability transition pore (mPTP). Mitochondria are central mediators of cell death and are implicated in most if not all neurodegenerative diseases regardless of the initiating factor: genetic mutations, excitotoxicity, reactive oxygen species, ischemia, chemical toxicity, etc. Mitochondria play diverse roles in all cells. In neurons, especially near synaptic sites, mitochondria are essential calcium-buffering organelles in areas where membrane excitability leads to large influx of calcium through calcium channels. Mitochondria also produce the ATP necessary for microtubule-based axoplasmic transport and maintaining the activity of ion and nutrient transporters. If a neuron fails to establish or maintain its functional role, mitochondria are responsible for eliminating it by releasing apoptotic factors. Olesoxime, by interacting with protein components of the mPTP, prevents the release of these apoptotic factors and therefore protects the neuron. This mechanism of action may lead to a general neuroprotective activity with utility in other therapeutic indications. |
| Molecular Formula |
C27H45NO
|
|---|---|
| Molecular Weight |
399.6523
|
| Exact Mass |
399.35
|
| Elemental Analysis |
C, 81.14; H, 11.35; N, 3.50; O, 4.00
|
| CAS # |
22033-87-0
|
| PubChem CID |
76971721
|
| Appearance |
Typically exists as white to off-white solids at room temperature
|
| Density |
1.1
|
| Boiling Point |
510ºC at 760mmHg
|
| Melting Point |
145-148ºC
|
| Flash Point |
341ºC
|
| Vapour Pressure |
1.56E-12mmHg at 25°C
|
| Index of Refraction |
1.583
|
| LogP |
7.858
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
29
|
| Complexity |
663
|
| Defined Atom Stereocenter Count |
7
|
| SMILES |
C[C@@]12C(CC[C@]3([H])[C@]2([H])CC[C@@]4(C)[C@@]3([H])CC[C@@]4([C@]([H])(C)CCCC(C)C)[H])=CC(CC1)=NO
|
| 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
|
| Chemical Name |
(8S,9S,10R,13R,14S,17R,E/Z)-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
|
| Synonyms |
E/Z-olesoxime; NSC 21311; NSC-21311; NSC21311; TRO-19622; TRO19622; TRO19622; RG6083; RG 6083; RG-6083;Olesoxime; Olesoxime, Z-; 22033-87-0; UNII-I2QN18P645; I2QN18P645; 66514-00-9; TRO 19622; (NE/Z)-N-[(8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-[(2R)-6-methylheptan-2-yl]-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ylidene]hydroxylamine;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~125.11 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5022 mL | 12.5109 mL | 25.0219 mL | |
| 5 mM | 0.5004 mL | 2.5022 mL | 5.0044 mL | |
| 10 mM | 0.2502 mL | 1.2511 mL | 2.5022 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA