AR7
目录号 : GC19035
AR7是一种非典型视黄酸受体α（RARα）拮抗剂。
Cas No.:80306-38-3
Sample solution is provided at 25 µL, 10mM.
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AR7 is an atypical retinoic acid receptor α (RARα) antagonist [1]. AR7 antagonizes RARα to relieve its inhibition of CMA, thereby significantly enhancing LAMP2A and CMA activity and promoting the selective degradation of misfolded or aggregated proteins [2-3]. AR7 is commonly used to treat Parkinson's disease [4].
In primary cortical neurons, AR7 (0-20μM; 21d) attenuates the progressive accumulation of intracellular and extracellular SNCA oligomers in long-term cultures of cortical neurons [5]. In SN4741 cells, AR7 (20μM; 24h) reduces lipid droplet accumulation in the Wdr45-deficient model by activating chaperone-mediated autophagy (CMA) and promoting the degradation of the lipid biosynthesis enzyme Fasn [6].
In C57BL/6 mice, AR7 (10mg/kg; ip; 6h) alleviates diclofenac-induced hepatic steatosis [7]. In heterozygous offspring mice, administration of AR7 (10mg/kg; ip; 6 weeks) promotes hepatic SERPINA1E342K/ATZ elimination and mitigates hepatic SERPINA1E342K/ATZ aggregation pathology [8].
References:
[1]. Anguiano J, Garner T P, Mahalingam M, et al. Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives[J]. Nature chemical biology, 2013, 9(6): 374-382.
[2]. Bourdenx M, Martín-Segura A, Scrivo A, et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome[J]. Cell, 2021, 184(10): 2696-2714. e25.
[3]. Wang Y T, Lu J H. Chaperone-mediated autophagy in neurodegenerative diseases: molecular mechanisms and pharmacological opportunities[J]. Cells, 2022, 11(14): 2250.
[4]. Chen J, Mao K, Yu H, et al. p38-TFEB pathways promote microglia activation through inhibiting CMA-mediated NLRP3 degradation in Parkinson's disease[J]. Journal of neuroinflammation, 2021, 18(1): 295.
[5]. Ho P W L, Leung C T, Liu H, et al. Age-dependent accumulation of oligomeric SNCA/α-synuclein from impaired degradation in mutant LRRK2 knockin mouse model of Parkinson disease: role for therapeutic activation of chaperone-mediated autophagy (CMA)[J]. Autophagy, 2020, 16(2): 347-370.
[6]. Xiong Q, Sun H, Wang Y, et al. Lipid droplet accumulation in Wdr45-deficient cells caused by impairment of chaperone-mediated autophagic degradation of Fasn[J]. Lipids in Health and Disease, 2024, 23(1): 91.
[7]. Lee W, Kim H Y, Choi Y J, et al. SNX10-mediated degradation of LAMP2A by NSAIDs inhibits chaperone-mediated autophagy and induces hepatic lipid accumulation[J]. Theranostics, 2022, 12(5): 2351.
[8]. Lin J, Wei X, Dai Y, et al. Chaperone-mediated autophagy degrades SERPINA1E342K/α1-antitrypsin Z variant and alleviates cell stress[J]. Autophagy, 2025: 1-18.
AR7是一种非典型视黄酸受体α（RARα）拮抗剂 [1]。AR7拮抗RARα以解除其对CMA的抑制，从而显著增强LAMP2A和CMA的活性，并促进错误折叠或聚集蛋白的选择性降解 [2-3]。AR7常用于治疗帕金森病 [4]。
在原代皮质神经元中，AR7（0-20μM：21d）可减弱长期培养皮质神经元细胞内和细胞外SNCA寡聚体的逐渐积累 [5]。在SN4741细胞中，AR7（20μM：24h）通过激活分子伴侣介导的自噬（CMA）并促进脂质生物合成酶Fasn的降解来减少Wdr45缺陷模型中的脂质滴积累 [6]。
在C57BL/6小鼠中，AR7（10mg/kg；ip；6h）可减轻diclofenac诱导的肝脏脂肪变性 [7]。在杂合子代小鼠中，给予AR7（10mg/kg；ip；6周）可促进肝脏SERPINA1E342K/ATZ消除，并减轻肝脏SERPINA1E342K/ATZ聚集病理 [8]。
| Cell experiment [1]: | |
Cell lines | Primary cortical neurons |
Preparation Method | To investigate whether AR7 treatment modulates SNCA oligomer levels, mature primary cortical neurons (DIV9) were cultured under normal conditions with or without AR7 (0, 10, or 20μM) for up to 21 days. AR7 dissolved in cell culture-grade DMSO was added to the culture medium at DIV9 and DIV14 at the indicated concentrations. Conditioned medium and total cell lysates were extracted at DIV9, 14, and 21 for Western blotting and SNCA oligomer ELISA analysis. |
Reaction Conditions | 0-20μM; 21d |
Applications | AR7 attenuates the progressive accumulation of intracellular and extracellular SNCA oligomers in long-term cultures of cortical neurons. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Male C57BL/6 mice (7 weeks old) were housed in an air-conditioned room (24℃) with a 12-hour day/night cycle and allowed free access to water and food for one week. After a one-week acclimation period, the animals were randomly divided into four groups (n=6 mice each): Group 1, vehicle; Group 2, diclofenac; Group 3, AR7; and Group 4, diclofenac + AR7. The vehicle group received an intraperitoneal injection of 0.5% DMSO in saline. The diclofenac group received diclofenac (100mg/kg, intraperitoneally) twice every 12 hours. The AR7 group received AR7 (10mg/kg, intraperitoneally) one hour before diclofenac. The following day, the mice were anesthetized with Zolettiline 50 and sacrificed. |
Dosage form | 10mg/kg; ip; 6h |
Applications | AR7 alleviates diclofenac-induced hepatic steatosis in vivo. |
References: | |
| Cas No. | 80306-38-3 | SDF | |
| Canonical SMILES | CC1=CC=C(C2=NC3=CC=C(Cl)C=C3OC2)C=C1 | ||
| 分子式 | C15H12ClNO | 分子量 | 257.71 |
| 溶解度 | DMSO : 25 mg/mL (97.01 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 3.8803 mL | 19.4017 mL | 38.8033 mL |
| 5 mM | 0.7761 mL | 3.8803 mL | 7.7607 mL |
| 10 mM | 0.388 mL | 1.9402 mL | 3.8803 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。
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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