CA77.1 是一种有效的，具有脑渗透性和口服活性的分子伴侣介导自噬 (CMA) 的 激活剂，表现出良好的药代动力学。CA77.1是 AR7 的衍生物，可以增加溶酶体受体 (LAMP2A) 在溶酶体中的表达。CA77.1 可以改善 PS19 小鼠模型的行为和神经病理特征，可用于阿尔茨海默病的研究。
货号:ajcx34596
CAS:2412270-22-3
分子式:C16H12ClN3O
分子量：297.74
溶解度:DMSO : 5 mg/mL (16.79 mM; ultrasonic and warming and heat to 60°C)|Ethanol :< 1 mg/mL (ultrasonic;warming;heat to 60°C) (insoluble)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

CA77.1 is a potent, brain-penetrant and orally active chaperone-mediated autophagy (CMA) activator with favorable pharmacokinetics. CA77.1 is a derivative of AR7 and can increase the expression of the lysosomal receptor LAMP2A in lysosomes. CA77.1 improves behavior and neuropathology in PS19 mice model and can be used for alzheimer’s disease research[1].

CA77.1 (0-30 μM; 16 hours) activates CMA in a dose-and time-dependent manner to NIH 3T3 cells stably expressing the KFERQ-PS-Dendra reporter. The CMA activity is quantified as the average of fluorescent puncta per cell[1].CA77.1 (20 μM; 6 hours) does not alter on LC3-II expression, and does not effects autophagic flux in NIH 3T3 cells[1].

CA77.1 (oral gavage; 10 mg/kg;single dose) demonstrates brain penetrance with favorable pharmacokinetics. The Cmax, AUClast, Tmax and T1/2 are 3534 ng/g, 8338 h*ng/g, 1 hour and 1.89 hour, respectively[1].CA77.1 (oral gavage; 30 mg/kg; 6 months) normalizes the previously described locomotor hyperactivity of PS19 mice to control levels. And it reduces the levels and number of neurons containing pathogenic tau conformations in the hippocampus, amygdala, and piriform cortex. And the higher number of microglial cells and presence of large Iba1-positive cells with rod-like dystrophic morphology in vehicle-treated PS19 mice are reduced upon CA77.1 treatment[1].

[1]. Mathieu Bourdenx, et al. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome.Cell. 2021 May 13;184(10):2696-2714.e25.