受注:045-509-1970 |
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Synonyms | AP23573 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C53H84NO14P |
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分子量 | 990.21 | CAS No. | 572924-54-0 | |
Solubility (25°C)* | 体外 | DMSO | 198 mg/mL (199.95 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | Ridaforolimus (Deforolimus, MK-8669, AP23573) is a selective mTOR inhibitor with IC50 of 0.2 nM in HT-1080 cell line; while not classified as a prodrug, mTOR inhibition and FKBP12 binding is similar to rapamycin. Phase 3. |
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in vitro | Treatment of HT-1080 cells with Deforolimus induces a dose-dependent inhibition of phosphorylation of both S6 and 4E-BP1, with IC50 of 0.2 nM and 5.6 nM, respectively, and leads to a decrease in cell size, an increase in the proportion of cells in the G1 phase of the cell cycle, and inhibition of glucose uptake. Deforolimus displays significant antiproliferative activity a broad panel of cell lines with EC50 of 0.2-2.3 nM. Deforolimus potently and selectively inhibits VEGF production in a dose-dependent manner. [1] Deforolimus treatment significantly induces growth suppression in human NSCLC cell lines with IC30 values of 2.45-8.83 nM, with the exception of H157 with IC30 of >20 nM. Deforolimus treatment (2.8-5.9 nM) significantly dephosphorylates p70S6KThr389 in A549, H1703 and H157 cells, except H1666 that may express a resistant variant of mTORC1, and causes increased phosphorylation of pAKTser473 and pAKTThr308 in A549 and H1703 cells. Deforolimus in combination with the MEK inhibitors, CI-1040 or PD0325901 exhibits dose-dependent synergism in lung cancer cell lines, which is associated with the suppression of proliferation rather than enhancement of cell death, involving the inhibition of ribosomal biogenesis by 40% within 24 hours and a decreased polysome/monosome ratio. [2] |
in vivo | Administration of Deforolimus exerts significant antitumor effects in mice bearing PC-3 (prostate), HCT-116 (colon), MCF7 (breast), PANC-1 (pancreas) or A549 (lung) xenografts in a dose-dependent manner, and inhibits mTOR signaling in in SK-LMS-1 xenograft model associated with inhibition of tumor growth. [1] |
キナーゼアッセイ | Cell based target inhibition | |
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HT-1080 cells are treated with increasing concentrations of Deforolimus (0-100 nM) for 2 hours, prior to harvest. Cellular lysates are extracted in denaturing lysis buffer, resolved on SDS-PAGE and transferred to PVDF membranes. After blocking, membranes are incubated with primary antibodies for 1 hour, followed by appropriate HRPconjugated secondary antibodies for 1 hour at room temperature. Immunoreactive proteins are detected using enhanced chemiluminescence and autoradiography performed by exposure to X-ray film. IC50 is determined from the inhibition of levels of phosphorylated ribosomal protein S6 (p-S6) and 4E-BP1 (p-4E-BP1). | ||
細胞アッセイ | 細胞株 | Colo205, H1755, H1395, H1666, A549, H157, and H1703 cells |
濃度 | Dissolved in ethanol, final concentrations ~ 1 μM | |
反応時間 | 72-120 hours | |
実験の流れ | Cells are seeded at 2-3 × 104/mL, and serial dilutions of Deforolimus are added after 2 hours, for at least three cell doublings (72-120 hours). Deforolimus effects are measured using the CellTiter 96 Aqueous nonradioactive cell proliferation assay and Sulforhodamine B assays. For Deforolimus, growth effects are described as IC30 because rapamycin and its derivatives do not significantly impede cell proliferation. |
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動物実験 | 動物モデル | Male and female athymic NCr-nu mice with xenografts established by subcutaneous implantation of PC-3, A549, HCT-116, MCF7, PANC-1 and SK-LMS-1 tumors |
投薬量 | ~10 mg/kg | |
投与方法 | Intraperitoneally |
, , Dr. Zhang of Tianjin Medical University
Data from [Data independently produced by , , Gynecol Oncol, 2016, 141(3):570-9]
Identification and evaluation of a lipid-lowering small compound in preclinical models and in a Phase I trial [ Cell Metab, 2022, 34(5):667-680.e6] | PubMed: 35427476 |
A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis [ Cell Metab, 2022, S1550-4131(22)00191-7] | PubMed: 35705079 |
Structural identification of lysophosphatidylcholines as activating ligands for orphan receptor GPR119 [ Nat Struct Mol Biol, 2022, (9):863-870.] | PubMed: 35970999 |
Molecular insights into biogenesis of glycosylphosphatidylinositol anchor proteins [ Nat Commun, 2022, 13(1):2617] | PubMed: 35551457 |
Extracellular vesicles from lung tissue drive bone marrow neutrophil recruitment in inflammation [ J Extracell Vesicles, 2022, 11(5):e12223] | PubMed: 35595717 |
Bladder Cancer-Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP-Related Metabolic Reprogramming and SerRS O-GlcNAcylation in Endothelial Cells [ Adv Sci (Weinh), 2022, e2202993] | PubMed: 36045101 |
CRISPR/Cas9 Screens Reveal that Hexokinase 2 Enhances Cancer Stemness and Tumorigenicity by Activating the ACSL4-Fatty Acid β-Oxidation Pathway [ Adv Sci (Weinh), 2022, 9(21):e2105126] | PubMed: 35603967 |
Global chromosome rearrangement induced by CRISPR-Cas9 reshapes the genome and transcriptome of human cells [ Nucleic Acids Res, 2022, 50(6):3456-3474] | PubMed: 35244719 |
USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy [ Autophagy, 2022, 1-13] | PubMed: 35900990 |
2AB protein of Senecavirus A antagonizes selective autophagy and type I interferon production by degrading LC3 and MARCHF8 [ Autophagy, 2022, 18(8):1969-1981] | PubMed: 34964697 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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