EasySep™小鼠TIL（CD45）正选试剂盒
产品号 #73232_C
mTOR通路抑制剂；抑制mTORC1和mTORC2复合物
若您需要咨询产品或有任何技术问题，请通过官方电话 400 885 9050 或邮箱 info.cn@stemcell.com 与我们联系
总览
Ku-0063794是一种细胞渗透性的，作用于丝氨酸-苏氨酸激酶哺乳动物雷帕霉素（mTOR）靶点的选择性抑制剂，同时抑制mTORC1和mTORC2复合物（IC₅₀= 10 nM）。它对76种其他蛋白激酶或7种脂质激酶（包括PI3激酶）具有良好的特异性（> 1000倍）（García-Martínez等人）。
维持
·通过保持线粒体氧化磷酸化，延长toll样受体（TLR）激活的树突状细胞的寿命（Amiel等人）。
癌症研究
·通过诱导 G1 期细胞周期阻滞，抑制小鼠胚胎成纤维细胞和人非小细胞肺癌细胞系的生长（García-Martínez 等人；Fei 等人）。
·在肾细胞癌异种移植模型中抑制肿瘤生长（Zhang等人）。
·在离体瘢痕疙瘩器官培养模型中减少瘢痕疙瘩（真皮纤维增生病变）体积，并在体外抑制瘢痕疙瘩细胞的扩散、增殖、迁移和侵袭性（Syed等人）。
细胞类型
癌细胞及细胞系，树突状细胞（DCs）
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
培养
研究领域
癌症
CAS 编号
938440-64-3
化学式
C₂₅H₃₁N₅O₄
纯度
≥98%
通路
mTOR
靶点
mTOR
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)
Mechanistic target of rapamycin inhibition extends cellular lifespan in dendritic cells by preserving mitochondrial function. Journal of immunology (Baltimore, Md. : 1950) 2014
Abstract
TLR-mediated activation of dendritic cells (DCs) is associated with a metabolic transition in which mitochondrial oxidative phosphorylation is inhibited by endogenously synthesized NO and the cells become committed to glucose and aerobic glycolysis for survival. We show that inhibition of mechanistic target of rapamycin (mTOR) extends the lifespan of TLR-activated DCs by inhibiting the induction of NO production, thereby allowing the cells to continue to use their mitochondria to generate ATP, and allowing them the flexibility to use fatty acids or glucose as nutrients to fuel core metabolism. These data provide novel mechanistic insights into how mTOR modulates DC metabolism and cellular longevity following TLR activation and provide an explanation for previous findings that mTOR inhibition enhances the efficacy of DCs in autologous vaccination.
Potent dual inhibitors of TORC1 and TORC2 complexes (KU-0063794 and KU-0068650) demonstrate in vitro and ex vivo anti-keloid scar activity. The Journal of investigative dermatology 2013
Abstract
Mammalian target of rapamycin (mTOR) is essential in controlling several cellular functions. This pathway is dysregulated in keloid disease (KD). KD is a common fibroproliferative dermal lesion with an ill-defined treatment strategy. KD demonstrates excessive matrix deposition, angiogenesis, and inflammatory cell infiltration. In KD, both total and phosphorylated forms of mTOR and p70(S6K)(Thr421/Ser424) are upregulated. Therefore, the aim of this study was to investigate adenosine triphosphate-competitive inhibitors of mTOR kinase previously unreported in keloid and their comparative efficacy with Rapamycin. Here, we present two mTOR kinase inhibitors, KU-0063794 and KU-0068650, that target both mTORC1 and mTORC2 signaling. Treatment with either KU-0063794 or KU-0068650 resulted in complete suppression of Akt, mTORC1, and mTORC2, and inhibition of keloid cell spreading, proliferation, migration, and invasive properties at a very low concentration (2.5 μmol l(-1)). Both KU-0063794 and KU-0068650 significantly (Ptextless0.05) inhibited cell cycle regulation and HIF1-α expression compared with that achieved with Rapamycin alone. In addition, both compounds induced shrinkage and growth arrest in KD, associated with the inhibition of angiogenesis, induction of apoptosis, and reduction in keloid phenotype-associated markers. In contrast, Rapamycin induced minimal antitumor activity. In conclusion, potent dual mTORC1 and mTORC2 inhibitors display therapeutic potential for the treatment of KD.
A comparison of Ku0063794, a dual mTORC1 and mTORC2 inhibitor, and temsirolimus in preclinical renal cell carcinoma models. PloS one 2013
Abstract
Rapamycin analogs, temsirolimus and everolimus, are approved for the treatment of advance renal cell carcinoma (RCC). Currently approved agents inhibit mechanistic target of rapamycin (mTOR) complex 1 (mTORC1). However, the mTOR kinase exists in two distinct multiprotein complexes, mTORC1 and mTORC2, and both complexes may be critical regulators of cell metabolism, growth and proliferation. Furthermore, it has been proposed that drug resistance develops due to compensatory activation of mTORC2 signaling during treatment with temsirolimus or everolimus. We evaluated Ku0063794, which is a small molecule that inhibits both mTOR complexes. Ku0063794 was compared to temsirolimus in preclinical models for renal cell carcinoma. Ku0063794 was effective in inhibiting the phosphorylation of signaling proteins downstream of both mTORC1 and mTORC2, including p70 S6K, 4E-BP1 and Akt. Ku0063794 was more effective than temsirolimus in decreasing the viability and growth of RCC cell lines, Caki-1 and 786-O, in vitro by inducing cell cycle arrest and autophagy, but not apoptosis. However, in a xenograft model there was no difference in the inhibition of tumor growth by Ku0063794 or temsirolimus. A potential explanation is that temsirolimus has additional effects on the tumor microenvironment. Consistent with this possibility, temsirolimus, but not Ku0063794, decreased tumor angiogenesis in vivo, and decreased the viability of HUVEC (Human Umbilical Vein Endothelial Cells) cells in vitro at pharmacologically relevant concentrations. Furthermore, expression levels of VEGF and PDGF were lower in Caki-1 and 786-O cells treated with temsirolimus than cells treated with Ku0063794.
更多信息
| 种属 | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 938440-64-3 |
| Chemical Formula | C₂₅H₃₁N₅O₄ |
| 纯度 | ≥ 98% |
| Target | mTOR |
| Pathway | mTOR |
相关产品
