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GSK621

现货
Catalog No.
B6020
AMPK激动剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,390.00
Ship with 10-15 days
25mg
¥ 4,890.00
Ship with 10-15 days

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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.

文献引用

1. Leeanna El-Houjeiri, Elite Possik, et al. "The transcription factors TFEB and TFE3 link the FLCN-AMPK signaling axis to innate immune response and pathogen resistance."bioRxiv. 2018 November 6.

Chemical Properties

Physical AppearanceA crystalline solid
StorageStore at 2-8°C
M.Wt489.91
Cas No.1346607-05-3
FormulaC26H20ClN3O5
SolubilitySoluble in DMSO
Chemical Name6-chloro-5-(2'-hydroxy-3'-methoxy-[1,1'-biphenyl]-4-yl)-3-(3-methoxyphenyl)-1H-pyrrolo[3,2-d]pyrimidine-2,4(3H,5H)-dione
SDFDownload SDF
Canonical SMILESCOC1=CC=CC(C2=CC=C(N3C(Cl)=CC(NC(N4C5=CC=CC(OC)=C5)=O)=C3C4=O)C=C2)=C1O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

MV4-11、OCI-AML3、OCI-AML2、HL-60、Kasumi、HEL、UT7、NB4、TF-1、KG1A、Nomo p28、SKM-1、U937、YHP1、MOLM-14、Mo7e、K562、MOLM-13、EOL-1和SET-2细胞系

制备方法

该化合物可溶于DMSO。若配制更高浓度的溶液,一般步骤如下:请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。

反应条件

30 μM;4天

实验结果

在20种细胞系中,GSK621抑制所有20种细胞的增殖,其IC50值范围为13 ~ 30 μM,同时促进17种细胞系凋亡。

动物实验 [1]:

动物模型

携带MOLM-14细胞异种移植瘤的小鼠

给药剂量

10或30 mg/kg;腹腔注射;每天2次

实验结果

在携带MOLM-14细胞异种移植瘤的小鼠中,GSK621(30 mg/kg;腹腔注射;每天2次)抑制白血病发展,并显著延长存活期。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[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.

质量控制

质量控制和MSDS

批次:

化学结构

GSK621

相关生物数据

GSK621