EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #72942_C
PI3K/AKT通路抑制剂；抑制AKT1、AKT2、AKT3
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总览
AKT抑制剂VIII是一种可透过细胞膜的变构性抑制剂，能够抑制三种AKT激酶（AKT1、AKT2和AKT3），IC₅₀值分别为58、 210和2200 nM (Lindsley et al.; Calleja et al.)。它对70种其他激酶具有良好的选择性，仅对部分激酶（如钙/钙调蛋白依赖性蛋白激酶 1 和平滑肌肌球蛋白轻链激酶）在微摩尔浓度下具有抑制作用（Logie et al.）。
癌症研究
·增强前列腺肿瘤细胞和宫颈癌细胞对凋亡刺激的敏感性（DeFeo-Jones et al.）。
·阻断有丝分裂并抑制HeLa细胞的迁移（Jo et al.）。
代谢
·减少肝细胞中胰岛素依赖基因的抑制，导致胰岛素敏感性降低（Logie et al.）。
细胞类型
癌细胞及细胞系，肝细胞
种属
人，小鼠，非人灵长类，其他物种，大鼠
研究领域
癌症，疾病建模
CAS 编号
612847-09-3
化学式
C₃₄H₂₉N₇O
纯度
≥98%
通路
PI3K/AKT
靶点
AKT1，AKT2，AKT3
产品说明书及文档
请在《产品说明书》中查找相关支持信息和使用说明，或浏览下方更多实验方案。
相关材料与文献
技术资料 (2)
文献 (5)
Allosteric Akt (PKB) inhibitors: discovery and SAR of isozyme selective inhibitors.
Bioorganic & medicinal chemistry letters 2005
Abstract
This letter describes the development of two series of potent and selective allosteric Akt kinase inhibitors that display an unprecedented level of selectivity for either Akt1,Akt2 or both Akt1/Akt2. An iterative analog library synthesis approach quickly provided a highly selective Akt1/Akt2 inhibitor that induces apoptosis in tumor cells and inhibits Akt phosphorylation in vivo.
Tumor cell sensitization to apoptotic stimuli by selective inhibition of specific Akt/PKB family members.
Molecular cancer therapeutics 2005 FEB
Abstract
Recent studies indicate that dysregulation of the Akt/PKB family of serine/threonine kinases is a prominent feature of many human cancers. The Akt/PKB family is composed of three members termed Akt1/PKBalpha,Akt2/PKBbeta,and Akt3/PKBgamma. It is currently not known to what extent there is functional overlap between these family members. We have recently identified small molecule inhibitors of Akt. These compounds have pleckstrin homology domain-dependent,isozyme-specific activity. In this report,we present data showing the relative contribution that inhibition of the different isozymes has on the apoptotic response of tumor cells to a variety of chemotherapies. In multiple cell backgrounds,maximal induction of caspase-3 activity is achieved when both Akt1 and Akt2 are inhibited. This induction is not reversed by overexpression of functionally active Akt3. The level of caspase-3 activation achieved under these conditions is equivalent to that observed with the phosphatidylinositol-3-kinase inhibitor LY294002. We also show that in different tumor cell backgrounds inhibition of mammalian target of rapamycin,a downstream substrate of Akt,is less effective in inducing caspase-3 activity than inhibition of Akt1 and Akt2. This shows that the survival phenotype conferred by Akt can be mediated by signaling pathways independent of mammalian target of rapamycin in some tumor cell backgrounds. Finally,we show that inhibition of both Akt1 and Akt2 selectively sensitizes tumor cells,but not normal cells,to apoptotic stimuli.
Characterization of a protein kinase B inhibitor in vitro and in insulin-treated liver cells.
Diabetes 2007
Abstract
OBJECTIVE: Abnormal expression of the hepatic gluconeogenic genes (glucose-6-phosphatase [G6Pase] and PEPCK) contributes to hyperglycemia. These genes are repressed by insulin,but this process is defective in diabetic subjects. Protein kinase B (PKB) is implicated in this action of insulin. An inhibitor of PKB,Akt inhibitor (Akti)-1/2,was recently reported; however,the specificity and efficacy against insulin-induced PKB was not reported. Our aim was to characterize the specificity and efficacy of Akti-1/2 in cells exposed to insulin and then establish whether inhibition of PKB is sufficient to prevent regulation of hepatic gene expression by insulin. RESEARCH DESIGN AND METHODS: Akti-1/2 was assayed against 70 kinases in vitro and its ability to block PKB activation in cells exposed to insulin fully characterized. RESULTS: Akti-1/2 exhibits high selectivity toward PKBalpha and PKBbeta. Complete inhibition of PKB activity is achieved in liver cells incubated with 1-10 mumol/l Akti-1/2,and this blocks insulin regulation of PEPCK and G6Pase expression. Our data demonstrate that only 5-10% of maximal insulin-induced PKB is required to fully repress PEPCK and G6Pase expression. Finally,we demonstrate reduced insulin sensitivity of these gene promoters in cells exposed to submaximal concentrations of Akti-1/2; however,full repression of the genes can still be achieved by high concentrations of insulin. CONCLUSIONS: This work establishes the requirement for PKB activity in the insulin regulation of PEPCK,G6Pase,and a third insulin-regulated gene,IGF-binding protein-1 (IGFBP1); suggests a high degree of functional reserve; and identifies Akti-1/2 as a useful tool to delineate PKB function in the liver.
更多信息
| 物种 | 人, 其它物种, 大鼠, 小鼠, 非人灵长类 |
|---|---|
| Cas Number | 612847-09-3 |
| Chemical Formula | C₃₄H₂₉N₇O |
| 纯度 | ≥ 98% |
| Target | AKT1, AKT2, AKT3 |
| Pathway | PI3K/AKT |
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