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 信号传导的抑制，溶酶体酸化增加和自噬激活。EN6 以溶酶体依赖性方式清除 TDP-43 聚集物，这是额颞叶痴呆的致病因子。
CAS：1808714-73-9
分子式：C19H14F2N4O2
分子量：368.34
纯度：98%
存储：Store at -20°C

Background:

EN6 is a small-molecule in vivo activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal the vacuolar H+ ATPase (v-ATPase). EN6-mediated ATP6V1A modification decouples the v-ATPase from the Rags, leading to inhibition of mTORC1 signaling, increased lysosomal acidification and activation of autophagy. EN6 clears TDP-43 aggregates, a causative agent in frontotemporal dementia, in a lysosome-dependent manner[1].

[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.