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GSK621
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
GSK621图片
CAS NO:1346607-05-3
规格:98%
分子量:489.91
包装与价格:
包装价格(元)
5mg电议
25mg电议

产品介绍
AMPK agonist
CAS:1346607-05-3
分子式:C26H20ClN3O5
分子量:489.91
纯度:98%
存储:Store at -20°C

Background:

GSK621 is a specific and potent agonist of AMP-activated protein kinase (AMPK) with IC50 values ranging from 13 to 30 μM for cell lines [1].


AMPK is a heterotrimeric serine/threonine kinase. It is a sensor of cellular energy. It regulates multiple cellular metabolic pathways. Activation of AMPK inactivates the phosphorylation of acetyl-Coa carboxylase (ACC), and hence inhibits the biosynthesis of fatty acid. Activation of AMPK also inhibits protein synthesis that is dependent on mammalian target of rapamycin complex 1. AMPK also promotes autophagy, fatty acid oxidation, glucose uptake and glycolysis [1].


In cells, at the opposite, GSK621 showed more potency to activate AMPK than A-769662, based on the ACC phosphorylation level. In MOLM-14 cells, 200 μM A-769662 is just as potent as 30 μM GSK621 to induce the phosphorylation of ULK1 (S555) and ACC (S79), two direct AMPK substrates. In AML cell lines (OCI-AML3, HL-60 and MOLM-14) and primary AML samples, the phosphorylation at AMPKα T172, a marker of AMPK activation, was markedly increased, and the phosphorylation of ULK1 (S555) and ACC (S79) was stimulated by GSK621 [1].


In animals with xenograft MOLM-14 cells, intraperitoneal injection of GSK621 at 30 mg/kg twice daily reduced leukemia growth and markedly extended survival compared to treatment with 10 mg/kg GSK621 twice daily or vehicle. These results correlated to increased AMPK activity indicated by the induction of apoptosis and increased ACC S79 phosphorylation [1].


Reference:
[1].? Sujobert P, Poulain L, Paubelle E, et al. Co-activation of AMPK and mTORC1 induces cytotoxicity in acute myeloid leukemia. Cell reports, 2015, 11(9): 1446-1457.