GSK621

GSK621 is a specific AMPK activator, with IC50 values of 13-30 μM for AML cells. GSK621 induces autophagy and apoptosis. GSK621 induces eiF2α phosphorylation-a hallmark of UPR activation[1].

Signaling Pathways >> Epigenetics >> AMPK

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

GSK621 (30 μM) induces AMPKα T172, ACC (S79) and ULK1 (S555) phosphorylation[1]. GSK621 (30 μM) induces autophagy and apoptosis[1]. GSK621 treatment also induces PERK phosphorylation, a marker of ER stress, in AML cells[1]. Cell Proliferation Assay[1] Cell Line: 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 AML cell lines.0-30 μM. Concentration: 0-30 μM. Incubation Time: 4 d. Result: IC50 values ranged from 13 to 30 μM. Reduced the proliferation of all 20 lines and increased apoptosis in 17 (85%) lines. Cell Autophagy Assay[1]. Cell Line: AML cell lines and primary AML samples. Concentration: 30 μM. Incubation Time: 24 h. Result: Induced the formation of numerous intracytoplasmic vacuoles including autophagosomes.

GSK621 (30 mg/kg, ip twice daily) exhibits significant anti-tumor activity in MOLM-14 cells xenograft[1]. Animal Model: MOLM-14 cells xenografted into nude mice[1]. Dosage: 30 mg/kg. Administration: IP twice daily. Result: Reduced leukemia growth and significantly extended survival compared to vehicle-treated animals or those treated with 10 mg/kg twice daily.

[1]. Pierre Sujobert, et al. Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia. Cell Rep. 2015 Jun 9;11(9):1446-57.