• 产品描述： 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

• 靶点： Autophagy;Protonpump; Autophagy

• 体外研究：
  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. 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 %

• 体内研究：
  EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy 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.

• 参考文献：
  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.

• 溶解性： Soluble  in  DMSO、Ethanol

• 保存条件： -20°C

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.715 ml	13.574 ml	27.149 ml
  5 mM	0.543 ml	2.715 ml	5.43 ml
  10 mM	0.271 ml	1.357 ml	2.715 ml
  50 mM	0.054 ml	0.271 ml	0.543 ml

• 注意：部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *