EN6

SKU: orb1218595

Description

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. 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).

Key Properties

• CAS Number: 1808714-73-9
• MW: 368.34
• Purity: >98% (HPLC)
• Formula: C₁₉H₁₄F₂N₄O₂
• SMILES: C=CC(Nc(cc(cc1)NC(c2cn(-c(cccc3)c3F)nc2)=O)c1F)=O
• Target: Others
• Solubility: DMSO: 4.63 mg/mL (12.57 mM; Need ultrasonic); Ethanol: 1.10 mg/mL (2.99 mM; ultrasonic and warming and heat to 60°C)

Bioactivity

• In Vivo:
  Animal model: Six-week-old male C57BL/6 mice. Dosage: 50 mg/kg. Administration: Intraperitoneal injection; single. Result: Significantly inhibited mTORC1 signaling in both skeletal muscle and heart, as demonstrated by reduced phosphorylation of S6, 4EBP1 and ULK1.Strongly activated autophagy as shown by heightened LC3BII levels and reduced p62 levels.
• In Vitro:
  Western blot analysis. Cell line: HEK293A cells. Concentration: 50 μM. Incubation time: 1, 4, 8 h. Result: Time- and dose-dependently triggered formation of LC3 puncta and increased the levels of LC3BII. Western blot analysis. Cell line: HEK293A cells. Concentration: 25 μM. Incubation time: 1 h. Result: Led to complete inactivation of mTORC1 signaling, as shown by reduced levels of phosphorylated canonical substrates, S6 kinase 1 (S6K1), 4EBP1, and ULK1. Immunofluorescence Cell line: HEK293A cells. Concentration: 50 μM. Incubation time: 4 h. Result: Led to significantly increased acidification of the lysosome in HEK293A cells, and this heightened acidification was blocked by BafA1.Immunofluorescence Cell line: IPTG-inducible GFP-TDP43 U2OS osteosarcoma cell line model. Concentration: 25 μM. Incubation time: 7 h. Result: Reduced IPTG-induced TDP43 aggregates by 75 %.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

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