产品号 #72952_C
PI3K/AKT通路抑制剂；抑制AKT
总览
AKT抑制剂X是一种可透过细胞膜的酚噁嗪衍生物，能够抑制 AKT 激酶的磷酸化，IC₅₀为~1 - 2 μM。该抑制剂可阻断AKT 在胰岛素样生长因子 1（IGF-1）处理后的易位（Thimmaiah et al.）。本产品以的盐酸盐形式供应。
癌症研究
·抑制人横纹肌肉瘤细胞系生长并诱导细胞凋亡（Thimmaiah et al.）。
·单独或与氯喹协同可抑制乳腺癌细胞系的增殖（Hu et al.）。
·减少黏液瘤病毒在多种人类肿瘤细胞系中的复制（Werden & McFadden）。
疾病建模
·诱导神经元自噬，并在亨廷顿病原代神经元细胞模型中发挥神经保护作用（Tsvetkov et al.）。
细胞类型
癌细胞及细胞系，乳腺细胞，神经元
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
研究领域
癌症，疾病建模，神经科学
CAS 编号
925681-41-0
化学式
C₂₀H₂₅ClN₂O · HCl
纯度
≥ 95 %
通路
PI3K/AKT
靶点
AKT
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Resources and Publications
Educational Materials (2)
Publications (4)
Pharmacological manipulation of the akt signaling pathway regulates myxoma virus replication and tropism in human cancer cells. Journal of virology 2010
Abstract
Viruses have evolved an assortment of mechanisms for regulating the Akt signaling pathway to establish a cellular environment more favorable for viral replication. Myxoma virus (MYXV) is a rabbit-specific poxvirus that encodes many immunomodulatory factors, including an ankyrin repeat-containing host range protein termed M-T5 that functions to regulate tropism of MYXV for rabbit lymphocytes and certain human cancer cells. MYXV permissiveness in these human cancer cells is dependent upon the direct interaction between M-T5 and Akt, which has been shown to induce the kinase activity of Akt. In this study, an array of compounds that selectively manipulate Akt signaling was screened and we show that only a subset of Akt inhibitors significantly decreased the ability of MYXV to replicate in previously permissive human cancer cells. Furthermore, reduced viral replication efficiency was correlated with lower levels of phosphorylated Akt. In contrast, the PP2A-specific phosphatase inhibitor okadaic acid promoted increased Akt kinase activation and rescued MYXV replication in human cancer cells that did not previously support viral replication. Finally, phosphorylation of Akt at residue Thr308 was shown to dictate the physical interaction between Akt and M-T5, which then leads to phosphorylation of Ser473 and permits productive MYXV replication in these human cancer cells. The results of this study further characterize the mechanism by which M-T5 exploits the Akt signaling cascade and affirms this interaction as a major tropism determinant that regulates the replication efficiency of MYXV in human cancer cells.
A small-molecule scaffold induces autophagy in primary neurons and protects against toxicity in a Huntington disease model. Proceedings of the National Academy of Sciences of the United States of America 2010
Abstract
Autophagy is an intracellular turnover pathway. It has special relevance for neurodegenerative proteinopathies, such as Alzheimer disease, Parkinson disease, and Huntington disease (HD), which are characterized by the accumulation of misfolded proteins. Although induction of autophagy enhances clearance of misfolded protein and has therefore been suggested as a therapy for proteinopathies, neurons appear to be less responsive to classic autophagy inducers than nonneuronal cells. Searching for improved inducers of neuronal autophagy, we discovered an N(10)-substituted phenoxazine that, at proper doses, potently and safely up-regulated autophagy in neurons in an Akt- and mTOR-independent fashion. In a neuron model of HD, this compound was neuroprotective and decreased the accumulation of diffuse and aggregated misfolded protein. A structure/activity analysis with structurally similar compounds approved by the US Food and Drug Administration revealed a defined pharmacophore for inducing neuronal autophagy. This pharmacophore should prove useful in studying autophagy in neurons and in developing therapies for neurodegenerative proteinopathies.
The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine. Bioorganic & medicinal chemistry 2008
Abstract
This study was to evaluate the enhancement value of chloroquine (CQ) in cancer cell killing when used in combination with Akt inhibitors. The results showed that the combination of CQ and Akt inhibitors is much more effective than either one alone. Importantly, the CQ-mediated chemosensitization of cell killing effects by Akt inhibitors is cancer specific. In particular, when combined with 10 microM CQ, 1,3-dihydro-1-(1-((4-(6-phenyl-1H-imidazo[4,5-g]quinoxalin-7-yl)phenyl)methyl)-4-piperidinyl)-2H-benzimidazol-2-one (an Akt1 and 2 inhibitor; compound 8) killed cancer cells 10-120 times more effectively than normal cells. Thus, CQ is a very effective and cancer-specific chemosensitizer when used in combination with Akt inhibitors.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 925681-41-0 |
| Chemical Formula | C₂₀H₂₅ClN₂O · HCl |
| Purity | ≥ 95% |
| Target | AKT |
| Pathway | PI3K/AKT |
相关产品
-
LY294002PI3K/AKT通路抑制剂；抑制PI3K
-
AKT抑制剂VIIIPI3K/AKT通路抑制剂；抑制AKT1、AKT2、AKT3
-
GDC- 0941PI3K/AKT通路抑制剂；抑制I类PI3k
PRODUCTS ARE FOR RESEARCH USE ONLY AND NOT INTENDED FOR HUMAN OR ANIMAL DIAGNOSTIC OR THERAPEUTIC USES UNLESS OTHERWISE STATED. FOR ADDITIONAL INFORMATION ON QUALITY AT STEMCELL, REFER TO WWW.STEMCELL.COM/COMPLIANCE.
