产品号 #73362_C
抗生素；mTOR通路抑制剂；抑制FKBP-12
总览
雷帕霉素（Rapamycin）是一种大环内酯类抗生素和免疫抑制剂，可抑制哺乳动物雷帕霉素靶蛋白（mTOR）信号传导。它通过与胞浆FK结合蛋白12（FKBP-12）形成复合物发挥作用，而FKBP-12又可直接与mTOR复合物1（mTORC1）结合。其免疫抑制作用是通过抑制对T细胞增殖和激活至关重要的IL-2信号传导来实现的（Gibbons等；Kay等）。雷帕霉素对白色念珠菌和其他真菌具有抗真菌活性（Vézina 等）。
癌症研究
·体外抑制MDA-MB-468人乳腺癌细胞生长，并在小鼠异种移植模型体内抑制肿瘤生长（Akcakanat等）。
·诱导恶性胶质瘤细胞自噬（Takeuchi等）。
细胞类型
癌细胞及细胞系，乳腺细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
抗生素
研究领域
癌症
CAS 编号
53123-88-9
化学式
C₅₁H₇₉NO₁₃
纯度
≥ 95 %
通路
mTOR
靶点
FKBP-12
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 (3)
Publications (7)
Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells. Frontiers in immunology 2021
Abstract
Intronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4+ T lymphocytes of healthy controls. The biological function of ANKRD55, its role in the immune system, and cellular sources of expression other than lymphocytes remain uncharacterized. Here, we show that monocytes gain capacity to express ANKRD55 during differentiation in immature monocyte-derived dendritic cells (moDCs) in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). ANKRD55 expression levels are further enhanced by retinoic acid agonist AM580 but downregulated following maturation with interferon (IFN)-$\gamma$ and lipopolysaccharide (LPS). ANKRD55 was detected in the nucleus of moDC in nuclear speckles. We also analyzed the adjacent IL6ST, IL31RA, and SLC38A9 genes. Of note, in healthy controls, MS risk SNP genotype influenced ANKRD55 and IL6ST expression in immature moDC in opposite directions to that in CD4+ T cells. This effect was stronger for a partially correlated SNP, rs13186299, that is located, similar to the main MS risk SNPs, in an ANKRD55 intron. Upon analysis in MS patients, the main GWAS MS risk SNP rs7731626 was associated with ANKRD55 expression levels in CD4+ T cells. MoDC-specific ANKRD55 and IL6ST mRNA levels showed significant differences according to the clinical form of the disease, but, in contrast to healthy controls, were not influenced by genotype. We also measured serum sgp130 levels, which were found to be higher in homozygotes of the protective allele of rs7731626. Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo-DC) differentiation as a process potentially influenced by MS risk SNPs.
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.
Mammalian target of rapamycin: discovery of rapamycin reveals a signaling pathway important for normal and cancer cell growth. Seminars in oncology 2009 DEC
Abstract
Since the discovery of rapamycin, considerable progress has been made in unraveling the details of the mammalian target of rapamycin (mTOR) signaling network, including the upstream mechanisms that modulate mTOR signaling functions, and the roles of mTOR in the regulation of mRNA translation and other cell growth-related responses. mTOR is found in two different complexes within the cell, mTORC1 and mTORC2, but only mTORC1 is sensitive to inhibition by rapamycin. mTORC1 is a master controller of protein synthesis, integrating signals from growth factors within the context of the energy and nutritional conditions of the cell. Activated mTORC1 regulates protein synthesis by directly phosphorylating 4E-binding protein 1 (4E-BP1) and p70S6K (S6K), translation initiation factors that are important to cap-dependent mRNA translation, which increases the level of many proteins that are needed for cell cycle progression, proliferation, angiogenesis, and survival pathways. In normal physiology, the roles of mTOR in both glucose and lipid catabolism underscore the importance of the mTOR pathway in the production of metabolic energy in quantities sufficient to fuel cell growth and mitotic cell division. Several oncogenes and tumor-suppressor genes that activate mTORC1, often through the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, are frequently dysregulated in cancer. Novel analogs of rapamycin (temsirolimus, everolimus, and deforolimus), which have improved pharmaceutical properties, were designed for oncology indications. Clinical trials of these analogs have already validated the importance of mTOR inhibition as a novel treatment strategy for several malignancies. Inhibition of mTOR now represents an attractive anti-tumor target, either alone or in combination with strategies to target other pathways that may overcome resistance. The far-reaching downstream consequences of mTOR inhibition make defining the critical molecular effector mechanisms that mediate the anti-tumor response and associated biomarkers that predict responsiveness to mTOR inhibitors a challenge and priority for the field.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 53123-88-9 |
| Chemical Formula | C₅₁H₇₉NO₁₃ |
| Purity | ≥ 95% |
| Target | FKBP-12 |
| Pathway | mTOR |
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