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
Pyruvate dehydrogenase kinase PDK1 is a metabolic enzyme responsible for switching glucose metabolism from mitochondrial oxidation to aerobic glycolysis in cancer cells, a general hallmark of malignancy termed the Warburg effect. JX06 is a potent, selective and covalent inhibitor of PDK with IC50s of 49, 101 and 313 nM for PDK1, PDK2 and PDK3, respectively. In A549 cells, JX06 (0-0.6 μM; 72 hours) dose-dependently inhibited the cell growth, and JX06 (0.1-10 μM; 6-24 hours) inhibited PDHA1 phosphorylation in a time- and dose-dependent manner. JX06 (1-10 μM) increased glucose uptake and intracellular ATP level and reduced aerobic glycolysis determined by the lactate production. JX06 (1-10 μM; 24 hours) induced ROS generation in cancer cells with high extracellular acidification rate (ECAR)/ oxygen consumption rate (OCR). In A549 xenograft models, JX06 (40-80 mg/kg; i.p. for 21 days) inhibited tumor growth[2].
作用机制
JX06 forms a disulfide bond with the thiol group of a conserved cysteine residue (C240) based on recognition of a hydrophobic pocket adjacent to the ATP pocket of the PDK1 enzyme[2].
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