产品号 #100-0265_C
AMPK激动剂
总览
GSK621是腺苷酸活化蛋白激酶 (AMPK) 的特异性激动剂（Sujobert等人）。
肿瘤研究
·在急性髓性白血病（AML）细胞和原发性AML样本中，可增加AMPKα T172磷酸化，这是AMPK活化的标志物（Sujobert等人）。
·通过eIF2信号通路激活自噬，能够在AML细胞系而非正常的造血祖细胞中表现出选择性细胞毒性（IC₅₀= 13 - 30 μM），且不依赖于mTORC1的激活 (Sujobert 等人)。
·抑制人黑色素瘤细胞存活和增殖（Chen等人）。
研究领域
自噬，癌症
CAS 编号
1346607-05-3
化学式
C₂₆H₂₀ClN₃O₅
分子量
489.9 克/摩尔
纯度
≥98%
通路
AMPK
靶点
AMPK
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Publications (2)
AMPK activation by GSK621 inhibits human melanoma cells in vitro and in vivo. Biochemical and biophysical research communications 2016 nov
Abstract
Recent studies suggest that forced activation of AMP-activated protein kinase (AMPK) could inhibit melanoma cell proliferation. In this report, we evaluated the anti-melanoma cell activity by a novel small-molecular AMPK activator, GSK621. Treatment of GSK621 decreased survival and proliferation of human melanoma cells (A375, WM-115 and SK-Mel-2 lines), which was accompanied by activation of caspase-3/-9 and apoptosis. Reversely, caspase inhibitors attenuated GSK621-induced cytotoxicity against melanoma cells. Significantly, GSK621 was more potent than other AMPK activators (A769662, Compound 13 and AICAR) in inhibiting melanoma cells. Intriguingly, same GSK621 treatment was non-cytotoxic or pro-apoptotic against human melanocytes. Molecularly, we showed that activation of AMPK mediated GSK621's activity against melanoma cells. AMPK$\alpha$1 shRNA knockdown or dominant negative mutation (T172A) dramatically attenuated GSK621-induced melanoma cell lethality. Further studies revealed that MEK-ERK activation might be the primary resistance factor of GSK621. MEK-ERK inhibition, either genetically or pharmacologically, significantly sensitized melanoma cells to GSK-621. Remarkably, intraperitoneal (i.p.) injection of GSK621 inhibited A375 tumor growth in SCID mice. Co-administration of MEK-ERK inhibitor MEK162 further sensitized GSK621-induced anti-A375 tumor activity in vivo. Together, the results imply that targeted activation of AMPK by GSK621 inhibits melanoma cell survival and proliferation. MEK-ERK inhibition may further sensitize GSK621's anti-melanoma cell activity in vitro and in vivo.
Co-activation of AMPK and mTORC1 Induces Cytotoxicity in Acute Myeloid Leukemia. Cell reports 2015 jun
Abstract
AMPK is a master regulator of cellular metabolism that exerts either oncogenic or tumor suppressor activity depending on context. Here, we report that the specific AMPK agonist GSK621 selectively kills acute myeloid leukemia (AML) cells but spares normal hematopoietic progenitors. This differential sensitivity results from a unique synthetic lethal interaction involving concurrent activation of AMPK and mTORC1. Strikingly, the lethality of GSK621 in primary AML cells and AML cell lines is abrogated by chemical or genetic ablation of mTORC1 signaling. The same synthetic lethality between AMPK and mTORC1 activation is established in CD34-positive hematopoietic progenitors by constitutive activation of AKT or enhanced in AML cells by deletion of TSC2. Finally, cytotoxicity in AML cells from GSK621 involves the eIF2$\alpha$/ATF4 signaling pathway that specifically results from mTORC1 activation. AMPK activation may represent a therapeutic opportunity in mTORC1-overactivated cancers.
更多信息
| Molecular Weight | 489.9 g/mol |
|---|---|
| Cas Number | 1346607-05-3 |
| Chemical Formula | C₂₆H₂₀ClN₃O₅ |
| Purity | ≥ 98% |
| Target | AMPK |
| Pathway | AMPK |
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