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Purity: ≥98%
AR-7 (Atypical Retinoid 7) is a potent and selective retinoic acid receptor α (RARα) antagonist and an enhancer of the chaperone-mediated autophagy (CMA). CMA is contributory to cellular quality control and the cellular response to stress through the selective degradation of cytosolic proteins in lysosomes. A decrease in CMA activity occurs in aging and in age-related disorders such as neurodegenerative diseases and diabetes. Signaling through RARα inhibits CMA. AR7 was identified to significantly activates CMA activity in mouse fibroblasts. A marked increase in CMA-activating potency is found when AR7 and GR1 are combined, supporting their cooperative effect. Treatment with the transcriptional repressor Actinomycin D partially reduces the stimulatory effect of AR7 on CMA, consistent with transcriptional changes contributing to the upregulation of CMA. The chemical enhancement of CMA protects cells from oxidative stress and from proteotoxicity, supporting a potential therapeutic opportunity when reduced CMA contributes to cellular dysfunction and disease.
| ln Vitro |
In both WT and LRRK2R1441G KI mutant MEFs, treatment with RARA antagonist AR7 (20 μM; for 16 h) boosted lysosomal activity[1]. In NIH 3T3 cells, AR7 (10, 20, 30 uM; 12 hours) has no influence on macroautophagy[2]. By selectively degrading cytosolic proteins in lysosomes, chaperone-mediated autophagy (CMA) supports cellular quality control and the response of the cell to stress. Reduced CMA activity is a common feature of aging and age-related diseases. CMA is inhibited by signaling via the retinoic acid receptor alpha (RARα). Mouse fibroblasts with AR7 exhibit a considerable increase in CMA activity. Combining GR1 and AR7 results in a significant increase in CMA-activating potency, confirming their cooperative impact. The stimulatory effect of AR7 on CMA is partially reduced upon treatment with the transcriptional repressor Actinomycin D, which is consistent with transcriptional modifications that contribute to CMA upregulation[3].
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| References |
[1]. Philip Wing-Lok Ho, 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). Autophagy. 2020
[2]. Mathieu Bourdenx, et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell. 2021 May 13;184(10):2696-2714.e25. [3]. Anguiano J, et al. Chemical modulation of chaperone-mediated autophagy by retinoic acid derivatives. Nat Chem Biol. 2013 Jun;9(6):374-82. |
| Molecular Formula |
C15H12CLNO
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| Molecular Weight |
257.72
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| CAS # |
80306-38-3
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| SMILES |
CC1=CC=C(C2=NC3=CC=C(Cl)C=C3OC2)C=C1
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.70 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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 (9.70 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (9.70 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 | 3.8802 mL | 19.4009 mL | 38.8018 mL | |
| 5 mM | 0.7760 mL | 3.8802 mL | 7.7604 mL | |
| 10 mM | 0.3880 mL | 1.9401 mL | 3.8802 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.
Effect of knockdown of RARα on autophagic pathways.Nat Chem Biol.2013 Jun;9(6):374-82. |
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Effect of ATRA on autophagy.Nat Chem Biol.2013 Jun;9(6):374-82. |
Design, synthesis and molecular docking of RARα-targeting compounds.Nat Chem Biol.2013 Jun;9(6):374-82. |
Effect of the chemical activators of CMA on RARα activity.Nat Chem Biol.2013 Jun;9(6):374-82. |
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Characterization of the effect of the retinoid derivatives on CMA.Nat Chem Biol.2013 Jun;9(6):374-82. |
Effect of the retinoid derivatives in the cellular response against different stressors.Nat Chem Biol.2013 Jun;9(6):374-82. |
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