Rapamycin

Antibiotic; mTOR pathway inhibitor; Inhibits FKBP-12

Rapamycin

Antibiotic; mTOR pathway inhibitor; Inhibits FKBP-12

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Antibiotic; mTOR pathway inhibitor; Inhibits FKBP-12
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Overview

Rapamycin is a macrolide antibiotic and immunosuppressive compound that inhibits mammalian target of rapamycin (mTOR) signaling. It acts through formation of a complex with cytosolic FK-binding protein 12 (FKBP-12), which directly binds to mTOR complex 1 (mTORC1). Its immunosuppressive effects are mediated through inhibition of IL-2 signaling that is critical for T-cell proliferation and activation (Gibbons et al.; Kay et al.). Rapamycin shows antifungal activity against Candida albicans and other fungi (Vézina et al.)

CANCER RESEARCH
· Inhibits growth of MDA-MB-468 human breast cancer cells in vitro, and inhibits tumor growth in a mouse xenograft model in vivo (Akcakanat et al.).
· Induces autophagy in malignant glioma cells (Takeuchi et al.).
Cell Type
Cancer Cells and Cell Lines, Mammary Cells
Species
Human, Mouse, Non-Human Primate, Other, Rat
Application
Antibiotic
Area of Interest
Cancer
CAS Number
53123-88-9
Chemical Formula
C₅₁H₇₉NO₁₃
Purity
≥ 95%
Pathway
mTOR
Target
FKBP-12

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
Rapamycin
Catalog #
73362, 100-1050, 73364
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
Rapamycin
Catalog #
73362, 73364
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
Rapamycin
Catalog #
100-1050
Lot #
All
Language
English

Resources and Publications

Publications (7)

Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55-IL6ST Gene Region in Immature Dendritic Cells. J. Mena et al. 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. Amiel E et al. 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. Gibbons JJ et al. 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.