| Bioactivity | AR7 is an atypical RARA/RARα (retinoic acid receptor, alpha) antagonist. AR7 specifically activates chaperone-mediated-autophagy (CMA) activity without affecting macroautophagy[1]. | ||||||||||||
| Invitro | Treatment with RARA antagonist, AR7 (20 μM; for 16 h), increased lysosomal activity in WT and LRRK2R1441G KI mutant MEFs[1]. AR7 (10, 20, 30 uM; 12, 24 hours) has no effect on macroautophagy in NIH 3T3 cells[2]. Chaperone-mediated autophagy (CMA) contributes to cellular quality control and the cellular response to stress through the selective degradation of cytosolic proteins in lysosomes. Decrease in CMA activity occurs in aging and in age-related disorders. Signaling through the retinoic acid receptor alpha (RARα) inhibits CMA. AR7 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[3]. | ||||||||||||
| Name | AR7 | ||||||||||||
| CAS | 80306-38-3 | ||||||||||||
| Formula | C15H12ClNO | ||||||||||||
| Molar Mass | 257.71 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |