1808714-73-9

EN6 is an autophagy activator th at simultaneously upregulates lysosomal vacuolar H(+)-ATPase (v-ATPase) activity and induces its decoupling from the Rag GTPases by covalently targeting v-ATPase subunit ATP6V1A Cys277. EN6 blocks mTORC1 lysosomal recruitment & activation (1-4 hr 25 μM EN6 pretreatment prior to 10-min amino acids (AA) stimulation of AA-starived HEK293) and clears cellular TDP-43 aggregates (25 μM; U2OS with inducible TDP-43). When administered in mice in vivo (50 mg/kg ip.)EN6 inhibits mTORC1 signaling and activates autophagy in both skeletal muscle and heart tissue. Unlike bafilomycin A1 (BafA1)EN6 activatesbut not inhibits v-ATPase catalytic activity.

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