| Bioactivity | 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[1]. | ||||||||||||
| Invitro | 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[1].EN6 leads to significant increases in the number autophagosomes and autolysosomes in HEK293A cells[1].EN6 (25 μM; 1 h) blocks mTORC1 lysosomal localization and activation in HEK293A cells[1].EN6 (50 μM; 4 h) activates the v-ATPase and lysosome acidification in HEK293A cells[1].EN6 (25 μM; 7 h) promotes autophagic clearance of protein aggregates in IPTG-inducible GFP-TDP43 U2OS osteosarcoma cell line model[1]. Western Blot Analysis[1] Cell Line: | ||||||||||||
| In Vivo | EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy in vivo[1]. Animal Model: | ||||||||||||
| Name | EN6 | ||||||||||||
| CAS | 1808714-73-9 | ||||||||||||
| Formula | C19H14F2N4O2 | ||||||||||||
| Molar Mass | 368.34 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [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. |