GSK621

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Chemical Structure| 1346607-05-3 同义名 : -
CAS号 : 1346607-05-3
货号 : A704781
分子式 : C26H20ClN3O5
纯度 : 98+%
分子量 : 489.91
MDL号 : MFCD28502280
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

2% DMSO+30% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
描述 GSK621, a new thienopyridone deritate, is specific activator of AMPK that can activate ACC (S79) and ULK1 (S555) in MOLM-14 cells with IC50 of 30 μM[2]. GSK621 could induce cytotoxicity (with a median IC50 of 20 µM) by activating autophagy independent of mTORC1. Moreover, the researchers also found that AMPK activation and constitutive activation of the mTORC1 signaling pathway have a lethal interaction in a series of AML primary samples and cell lines, while constitutively activated mTORC1 is absent in normal hematopoietic progenitors, so AMPK activation does not cause toxic effects on normal cells[2]. There are also study demonstrate that GSK621 also can inhibit human melanoma cells A375 survival in both time- and concentration-dependent (1 μM – 3 μM) manners as well as pro-apoptotic activity[3]. In vivo, GSK621 (30 mg/kg twice daily) decreased leukemia growth and significantly prolonged survival of xenograft tumor mouse[4]. On the other hand, the oral administration of GSK621 inhibited the LPS-induced TNFα production and endotoxin shock in BALB/c mice[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.04mL

0.41mL

0.20mL

10.21mL

2.04mL

1.02mL

20.41mL

4.08mL

2.04mL
参考文献

[1]331(6016):456-61.

[2]Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, Asara JM, Fitzpatrick J, Dillin A, Viollet B, Kundu M, Hansen M, Shaw RJ. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011 Jan 28;331(6016):456-61.

[3]Chen L, Chen Q, Deng G, Kuang S, Lian J, Wang M, Zhu H. AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo. Biochem Biophys Res Commun. 2016 Nov 25;480(4):515-521.

[4]Sujobert P, Poulain L, Paubelle E, Zylbersztejn F, Grenier A, Lambert M, Townsend EC, Brusq JM, Nicodeme E, Decrooqc J, Nepstad I, Green AS, Mondesir J, Hospital MA, Jacque N, Christodoulou A, Desouza TA, Hermine O, Foretz M, Viollet B, Lacombe C, Mayeux P, Weinstock DM, Moura IC, Bouscary D, Tamburini J. Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia. Cell Rep. 2015 Jun 9;11(9):1446-57.