EN6|cas:1808714-73-9|西域试剂

EN6,99.16%

产品编号：Bellancom-128892| CAS NO：1808714-73-9| 分子式：C₁₉H₁₄F₂N₄O₂| 分子量：368.34

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	价格	库存与货期
Bellancom-128892	￥921.00	杭州北京（现货）
Bellancom-128892	￥1567.00	杭州北京（现货）
Bellancom-128892	￥3135.00	杭州北京（现货）
Bellancom-128892	￥4700.00	杭州北京（现货）

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EN6

产品介绍

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 信号的抑制，增加溶酶体酸化，并激活自噬。EN6 还能以溶酶体依赖的方式清除 TDP-43 聚集物 (额颞叶痴呆的致病因子)。

生物活性

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.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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
(In Vivo)

EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究

EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

体内研究

EN6 (50 mg/kg; i.p.; single) inhibits mTORC1 and activates autophagy in vivo.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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.

性状

Solid

溶解性数据

In Vitro:

DMSO : 5 mg/mL (13.57 mM; Need ultrasonic)

Ethanol : 1.11 mg/mL (3.01 mM; ultrasonic and warming and heat to 60°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	2.7149 mL	13.5744 mL	27.1488 mL
5 mM	0.5430 mL	2.7149 mL	5.4298 mL
10 mM	0.2715 mL	1.3574 mL	2.7149 mL

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶