OAB-14
目录号 : GC68377OAB-14 是一种 Bexarotene 衍生物，通过增加 APP/PS1 小鼠的 β-淀粉样蛋白清除率，改善阿尔茨海默病相关的病理学和认知障碍。OAB-14 可有效改善 APP/PS1 转基因小鼠内体自噬溶酶体途径的功能障碍。
Cas No.:2140911-49-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
OAB-14, is a Bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. OAB-14 effectively ameliorates the dysfunction of the endosomal-autophagic-lysosomal pathway in APP/PS1 transgenic mice[1][2].
OAB-14 significantly alleviates cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice after administration for 15 days or 3 months. OAB-14 rapidly cleared 71% of Aβ by promoting microglia phagocytosis and increasing IDE and NEP expression. OAB-14 also attenuates the downstream pathological events of Aβ accumulation, such as synaptic degeneration, neuronal loss, tau hyperphosphorylation and neuroinflammation in APP/PS1 mice. OAB-14 has no significant effect on body weight or liver toxicity after acute and chronic treatment[1].
OAB-14 facilitates receptor-mediated endocytosis and restores autophagy flux via the AMPK/mTOR pathway. OAB-14 enhances the lysosomal activity, and reduced Aβ accumulation in lysosomes is observed in OAB-14-treated AD mice[2].
[1]. Guo X, et al. OAB-14 Effectively Ameliorates the Dysfunction of the Endosomal-Autophagic-Lysosomal Pathway in APP/PS1 Transgenic Mice. ACS Chem Neurosci. 2021;12(21):3985-3993.
[2]. Yuan C, et al. OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice. Biochim Biophys Acta Mol Basis Dis. 2019;1865(1):161-180.
| Cas No. | 2140911-49-3 | SDF | Download SDF |
| 分子式 | C32H46N4O2 | 分子量 | 518.73 |
| 溶解度 | DMSO : 20 mg/mL (38.56 mM; ultrasonic and warming and adjust pH to 3 with HCl and heat to 60°C) | 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 | 1.9278 mL | 9.6389 mL | 19.2779 mL |
| 5 mM | 0.3856 mL | 1.9278 mL | 3.8556 mL |
| 10 mM | 0.1928 mL | 0.9639 mL | 1.9278 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。
1. 首先保证母液是澄清的；
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
OAB-14 Effectively Ameliorates the Dysfunction of the Endosomal-Autophagic-Lysosomal Pathway in APP/PS1 Transgenic Mice
ACS Chem Neurosci 2021 Nov 3;12(21):3985-3993.PMID:34652916DOI:10.1021/acschemneuro.1c00209.
In Alzheimer's disease (AD), damaged Aβ clearance contributes to elevated levels of Aβ that cause a series of cytotoxic cascade reactions. Thus, targeting Aβ clearance has now been considered a valid therapeutic approach for AD. Cellular uptake and degradation are important mechanisms for Aβ clearance, which are mainly performed by the endosomal-autophagic-lysosomal (EAL) pathway. Our previous study showed that OAB-14, a novel small molecule designed with bexarotene as the lead compound, treatment for 3 months significantly alleviated cognitive disorders and remarkably reduced the deposition of Aβ without affecting its production in APP/PS1 transgenic mice. Here, we further revealed that enhancement of the EAL activity is one of the mechanisms that increases Aβ clearance after OAB-14 administration for 3 months. OAB-14 facilitates receptor-mediated endocytosis and restores autophagy flux via the AMPK/mTOR pathway. Meanwhile, OAB-14 enhances the lysosomal activity, and reduced Aβ accumulation in lysosomes was observed in OAB-14-treated AD mice. These results suggest that OAB-14 may promote Aβ clearance in lysosomes by alleviating the EAL dysfunction in AD mice.
OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing β-amyloid clearance in APP/PS1 mice
Biochim Biophys Acta Mol Basis Dis 2019 Jan;1865(1):161-180.PMID:30389579DOI:10.1016/j.bbadis.2018.10.028.
The pathogenesis of Alzheimer's disease (AD) is complex, though the clinical failures of anti-AD candidates targeting Aβ production (such as β- and γ-secretase inhibitors) make people suspect the Aβ hypothesis, in which the neurotoxicity of Aβ is undoubtedly involved. According to studies, >95% of AD patients with sporadic AD are primarily associated with abnormal Aβ clearance. Therefore, drugs that increase Aβ clearance are becoming new prospects for the treatment of AD. Here, the novel small molecule OAB-14, designed using bexarotene as the lead compound, significantly alleviated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice after administration for 15 days or 3 months. OAB-14 rapidly cleared 71% of Aβ by promoting microglia phagocytosis and increasing IDE and NEP expression. This compound also attenuated the downstream pathological events of Aβ accumulation, such as synaptic degeneration, neuronal loss, tau hyperphosphorylation and neuroinflammation in APP/PS1 mice. Moreover, OAB-14 had no significant effect on body weight or liver toxicity after acute and chronic treatment. OAB-14 was well tolerated and its maximum-tolerated dose in mice was >4.0 g/kg. Based on these findings, OAB-14 represents a promising new candidate for AD treatment.