olesoxime | 22033-87-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: olesoxime
• 英文别名: Cholest-4-en-3-one, oxime, (3E)-；cholest-4-en-3-one oxime；Cholest-4-en-3-on (syn-oxim)；Cholest-4-en-3-on-oxim
• CAS: 22033-87-0；66514-00-9；66538-08-7
• 化学式: C₂₇H₄₅NO
• 分子量: 399.66
• InChiKey: QNTASHOAVRSLMD-IVFFKYSXSA-N

物化性质

• 熔点：
  145-148 ºC
• 沸点：
  510.0±23.0 °C(Predicted)
• 密度：
  1.10
• 溶解度：
  二甲基亚砜：>10mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  7.86
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  32.59
• 氢给体数：
  1.0
• 氢受体数：
  2.0

制备方法与用途

生物活性

Olesoxime (TRO 19622) 是一种靶向线粒体的神经保护性试剂，促进细胞存活，EC50 为 3.2±0.2 µM。

靶点

Mitochondrial

体外研究

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 EC ₅₀ 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%. 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.

体内研究

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. 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. 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.