There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
The vacuolar H+-ATPase (v-ATPase) is a universal component of eukaryotic organisms, which is present in both intracellular compartments and the plasma membrane. Its proton-pumping action creates the low intravacuolar pH, benefiting many processes such as, membrane trafficking, protein degradation, renal acidification, bone resorption, and tumor metastasis [1]. EN6 is a small-molecule activator of autophagy that covalently targets cysteine 277 in the ATP6V1A subunit of the lysosomal v-ATPase, which activates mechanistic target of rapamycin complex 1 (mTORC1) via the Rag guanosine triphosphatases. 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 [2].
作用机制
EN6 covalently binds to cysteine 277 in the ATP6V1A subunit of v-ATPase .
EN6 细胞实验
Cell Line
Concentration
Treated Time
Description
References
U2OS cells
25 μM
7 hours
EN6 treatment reduced TDP-43 aggregates by 75%, and this clearance was lysosome- and v-ATPase-dependent.
Nat Chem Biol. 2019 Aug;15(8):776-785
HEK293A cells
25 μM
4 hours
EN6 treatment significantly increased the formation of LC3 puncta, similar to Torin1 treatment.
Nat Chem Biol. 2019 Aug;15(8):776-785
HEK293A cells
50 μM
24 hours
EN6 treatment increased LC3B degradation to a comparable degree to direct mTORC1 inhibitors, rapamycin and Torin1.
Nat Chem Biol. 2019 Aug;15(8):776-785
Mycobacterium tuberculosis H37Rv
100 µg/mL
4 hours
Evaluate the inhibitory effect of DCS on M. tuberculosis, results showed DCS inhibits two enzymes: alanine racemase (Alr) and D-Ala:D-Ala ligase (Ddl)
Nat Commun. 2019 Sep 13;10(1):4177
EN6 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6 mice
Intraperitoneal (i.p.)
50 mg/kg
Single dose, analyzed after 4 h
EN6 treatment significantly inhibited mTORC1 signaling in skeletal muscle and heart and activated autophagy, as shown by increased LC3BII levels and reduced p62 levels.
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