TRO 19622
(Synonyms: 奥利索西,TRO 19622; NSC 21311) 目录号 : GC13726
A mitochondrial-targeted neuroprotective agent
Cas No.:22033-87-0
Sample solution is provided at 25 µL, 10mM.
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Olesoxime (TRO 19622) is a mitochondrial-targeted neuroprotective compound with mean EC50 value for increasing cell survival is 3.2±0.2 µM.
Exposure to Olesoxime (TRO 19622) (ranging from 0.1 to 10 µM) at 1 h after plating significantly protects primary embryonic rat spinal MNs (that had been cultured for 3 days without brain-derived, ciliary and glia-derived neurotrophic factors) from cell death. At a concentration of 10 µM, Olesoxime (TRO 19622) maintains survival of 74±10% of the neurons supported by a combination of neurotrophic factors (brain-derived, ciliary and glia-derived neurotrophic factors). The mean EC50 in this assay is 3.2±0.2 µM. In addition to preserving MN cell bodies, Olesoxime (TRO 19622) also promotes the outgrowth of neurites. At a concentration of 1 µM, which increases cell survival by only 38%, Olesoxime (TRO 19622) increases overall neurite outgrowth per cell by 54%[1]. Olesoxime (TRO 19622) belongs to a new family of cholesterol-oximes identified for its survival-promoting activity on purified motor neurons deprived of neurotrophic factors. Olesoxime (TRO 19622) targets proteins of the outer mitochondrial membrane, concentrates at the mitochondria and prevents permeability transition pore opening mediated by, among other things, oxidative stress[2].
Daily administration of Olesoxime (TRO 19622) (3 or 30 mg/kg sc) to adult mice for more than 2 months is well tolerated without toxicity or adverse effects[1]. When animals are treated orally for 5 days following the lesion, Olesoxime (TRO 19622) increases motor neuron cell body survival in a dose-dependent manner with significant rescue at the highest dose of 100 mg/kg. At this dose, motor neuron survival is 29 ±2% (n=18) corresponding to a 42% increase in survival compared with vehicle-treated animals[3]. Paclitaxel-treated rats that receive prophylactic treatment with 3 mg/kg/d or 30 mg/kg/d Olesoxime (TRO 19622) have 239±17.6 and 247±14.4 IENFs per cm, respectively. For both doses, the decreases are significantly less than the 46% decrease seen in the Paclitaxel-treated rats administered vehicle. However, both doses produce decreases (25% and 22%) that are significantly different relative to the naïve control group[4].
Reference:
[1]. Martin LJ, et al. Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Aug;13(8):568-80.
[2]. Bordet T, et al. Olesoxime (TRO19622): A Novel Mitochondrial-Targeted Neuroprotective Compound. Pharmaceuticals (Basel). 2010 Jan 28;3(2):345-368
[3]. Bordet T, et al. Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis. J Pharmacol Exp Ther. 2007 Aug;322(2):709-20.
[4]. Xiao WH, et al. 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. 2009 Dec 15;147(1-3):202-9
Animal experiment: | Mice[3] Eight-week-old C57bl/6 RJ mice are anesthetized using 60 mg/kg i.p. ketamine chlorohydrate. To reduce the risk of gender-related differences in response to Olesoxime (TRO 19622), only female mice are used. The right sciatic nerve is surgically exposed at mid-thigh level, and it is crushed 5 mm proximal to the trifurcation of the sciatic nerve. The nerve is crushed twice for 30 s with hemostatic forceps (width, 1.5 mm) with a 90° rotation between each crush. Sciatic nerve degeneration/regeneration is assessed over 6 weeks by measurement of the compound muscular action potential (CMAP) and histological studies of the damaged area of the sciatic nerve. Olesoxime (TRO 19622) is given subcutaneously at 0.3, 3, and 30 mg/kg. Treatments started the day of the crush injury, and they continued daily for 6 weeks. In total, 15 animals per group are used in the study. Electromyography is performed once a week for 6 weeks using a Neuromatic 2000M electromyograph. Mice are anesthetized using 100 mg/kg i.p. ketamine chlorohydrate. CMAP is measured in the gastrocnemius muscle after a single 0.2-ms stimulation of the sciatic nerve at supramaximal intensity (12.8 mA). The amplitude (millivolts) and the latency (milliseconds) of the action potential are measured. Rats[4] Adult male Sprague-Dawley rats (200-300 g) are used. Olesoxime (TRO 19622) or the vehicle is administered via oral gavage in a volume of 5 mL/kg. The TRO19622doses used here (3-100 mg/kg) are chosen based on prior reports of neuroprotective and analgesic activity. |
References: [1]. Martin LJ, et al. Olesoxime, a cholesterol-like neuroprotectant for the potential treatment of amyotrophic lateral sclerosis. IDrugs. 2010 Aug;13(8):568-80. | |
| Cas No. | 22033-87-0 | SDF | |
| 别名 | 奥利索西,TRO 19622; NSC 21311 | ||
| 化学名 | (8S,9S,10R,13R,14S,17R,E)-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one oxime | ||
| Canonical SMILES | CC(CCC[C@@]([C@@]1([H])CC[C@@]2([H])[C@]([C@]3([H])CC[C@]12C)([H])CCC4=C/C(CC[C@@]43C)=N/O)([H])C)C | ||
| 分子式 | C27H45NO | 分子量 | 399.65 |
| 溶解度 | DMF: 2 mg/ml,DMSO: 0.1 mg/ml,Ethanol: 20 mg/ml,Ethanol:PBS (pH 7.2)(1:2): 0.3 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
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2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet