EN6 是一种小分子体内自噬 (autophagy) 激活剂，其共价靶向溶酶体v-ATP 酶的 ATP6V1A 亚基中的半胱氨酸 277。EN6 介导的 ATP6V1A 修饰使 v-ATP 酶与 Rag 解偶联，导致 mTORC1 信号的抑制，增加溶酶体酸化，并激活自噬。EN6 还能以溶酶体依赖的方式清除 TDP-43 聚集物 (额颞叶痴呆的致病因子)。

EN6 is a small-molecule in vivo autophagy activator that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase. EN6-mediated modification of ATP6V1A uncouples v-ATPase from Rag, leading to inhibition of mTORC1 signalling, increased lysosomal acidification, and activation of autophagy. EN6 also scavenges TDP-43 aggregates (causative agents of frontotemporal dementia) in a lysosome-dependent manner.

Solid

EN6 (50 μM; 1, 4, 8 h) increases the levels of LC3BII, and triggers formation of LC3 puncta in a time- and dose-dependent manner, in HEK293A cells.
EN6 leads to significant increases in the number autophagosomes and autolysosomes in HEK293A cells.
EN6 (25 μM; 1 h) blocks mTORC1 lysosomal localization and activation in HEK293A cells.
EN6 (50 μM; 4 h) activates the v-ATPase and lysosome acidification in HEK293A cells.
EN6 (25 μM; 7 h) promotes autophagic clearance of protein aggregates in IPTG-inducible GFP-TDP43 U2OS osteosarcoma cell line model. has not independently confirmed the accuracy of these methods. They are for reference only.

EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy in vivo. has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Six-week-old male C57BL/6 mice.

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[1]. Chung CY, et al. Covalent targeting of the vacuolar H+-ATPase activates autophagy via mTORC1 inhibition. Nat Chem Biol. 2019 Aug;15(8):776-785.

In Vitro: DMSO : 5 mg/mL (13.57 mM; Need ultrasonic)Ethanol : 1.11 mg/mL (3.01 mM; ultrasonic and warming and heat to 60°C)配制储备液