AR7 is a retinoic acid receptor α (RARα) antagonist.
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HazMat fee for 500 gram (Estimated)
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USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
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Accessible (Haz class 3, 4, 5 or 8), International
Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are related to embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors[1]. Atypical retinoid 7 (AR7) is a retinoic acid receptor α (RARα) antagonist and also acts as chaperone-mediated autophagy (CMA) activator. AR7 dose-dependently activates CMA activity in mouse fibroblasts expressing the KFERQ-mcherry1 photoactivable reporter. In Parkinson disease, mutant LRRK2 perturbs chaperone-mediated-autophagy (CMA) to degrade α-synuclein. AR7 treatment in 24 h dose-dependently, induced neuronal LAMP2A transcription and lysosomal activity in mouse embryonic fibroblasts (MEFs). AR7 at 20 μM also attenuated the progressive accumulation of both intracellular and extracellular α-synuclein oligomers in prolonged cultures of mutant cortical neurons (DIV21), indicating that oligomer accumulation can be suppressed by CMA activation[2].
作用机制
AR-7 is docked to a hydrophobic region of the RARα-binding pocket formed by h3, h10 and h12[3].
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