product name GSK621
Description: GSK621 is a potent and selective AMPK agonist. GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. Cytotoxicity in AML cells from GSK621 involves the eIF2α/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
References: Cell Rep. 2015 Jun 9;11(9):1446-57.
489.91
Formula
C26H20ClN3O5
CAS No.
1346607-05-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 97 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393211
| In Vitro |
In vitro activity: In AML cell lines and primary AML samples, GSK621 markedly increases phosphorylation at AMPKα T172, a marker of AMPK activation. In a set of 20 cell lines, GSK621 reduces the proliferation of all 20 lines with IC50 ranged from 13-30 μM, and increases apoptosis in 17 (85%) lines. In addition, GSK621 also triggers autophagy, which partially contributes to AML cell death. Kinase Assay: HEPG2 cells are treated with increasing doses of A-769662 or GSK621, and ACC S79 phosphorylation is assessed as a surrogate marker for AMPK activation using a commercially available ELISA kit. Cell Assay: Twenty AML cell lines (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, SET-2 cell lines) are treated with log10 dilutions of GSK621 and relative viability is determined by CellTiter-Glo?assay. IC50 of GSK621 among these 20 cell lines is calculated using the Prism software and are presented as log[C] with [C] in mol/l (M). Results are presented for 5 different cell lines per panel. |
|---|---|
| In Vivo | In nude mice bearing MOLM-14 xenografts, GSK621 (30 mg/kg, i.p.) reduces leukemia growth and significantly extends survival by enhancing AMPK activity and the induction of apoptosis. |
| Animal model | In animals with xenograft MOLM-14 cells |
| Formulation & Dosage | 30 mg/kg; i.p. injection. |
| References | Cell Rep. 2015 Jun 9;11(9):1446-57. |
Related Posts
product name GSK621
Description: GSK621 is a potent and selective AMPK agonist. GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. Cytotoxicity in AML cells from GSK621 involves the eIF2α/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
References: Cell Rep. 2015 Jun 9;11(9):1446-57.
489.91
Formula
C26H20ClN3O5
CAS No.
1346607-05-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 97 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19393211
| In Vitro |
In vitro activity: In AML cell lines and primary AML samples, GSK621 markedly increases phosphorylation at AMPKα T172, a marker of AMPK activation. In a set of 20 cell lines, GSK621 reduces the proliferation of all 20 lines with IC50 ranged from 13-30 μM, and increases apoptosis in 17 (85%) lines. In addition, GSK621 also triggers autophagy, which partially contributes to AML cell death. Kinase Assay: HEPG2 cells are treated with increasing doses of A-769662 or GSK621, and ACC S79 phosphorylation is assessed as a surrogate marker for AMPK activation using a commercially available ELISA kit. Cell Assay: Twenty AML cell lines (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, SET-2 cell lines) are treated with log10 dilutions of GSK621 and relative viability is determined by CellTiter-Glo?assay. IC50 of GSK621 among these 20 cell lines is calculated using the Prism software and are presented as log[C] with [C] in mol/l (M). Results are presented for 5 different cell lines per panel. |
|---|---|
| In Vivo | In nude mice bearing MOLM-14 xenografts, GSK621 (30 mg/kg, i.p.) reduces leukemia growth and significantly extends survival by enhancing AMPK activity and the induction of apoptosis. |
| Animal model | In animals with xenograft MOLM-14 cells |
| Formulation & Dosage | 30 mg/kg; i.p. injection. |
| References | Cell Rep. 2015 Jun 9;11(9):1446-57. |