受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C12H8ClN3O3 |
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分子量 | 277.66 | CAS No. | 313516-66-4 | ||||
Solubility (25°C)* | 体外 | DMSO | 56 mg/mL (201.68 mM) | ||||
Water | Insoluble | ||||||
Ethanol | Insoluble | ||||||
体内 (毎回新しく調製した物を用意してください) |
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* <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 | T0070907 is a potent inhibitor of PPARγ (peroxisome proliferator activator receptor γ ) that induces G2/M arrest and enhances the effect of radiation in human cervical cancer cells through mitotic catastrophe. It also acts as an antagonist of PPARγ that suppresses breast cancer cell proliferation and motility via both PPARgamma-dependent and -independent mechanisms. |
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in vitro | T0070907 is a potent and selective PPARγ antagonist. With an apparent binding affinity (concentration at 50% inhibition of [3H] rosiglitazone binding or IC50) of 1 nM, T0070907 covalently modifies PPARγ on cysteine 313 in helix 3 of human PPARγ2. T0070907 blocks PPARγ function in both cell-based reporter gene and adipocyte differentiation assays. Consistent with its role as an antagonist of PPARγ, T0070907 blocks agonist-induced recruitment of coactivator-derived peptides to PPARγ in a homogeneous time-resolved fluorescence-based assay and promotes recruitment of the transcriptional corepressor NCoR to PPARγ in both glutathione S-transferase pull-down assays and a PPARγ/retinoid X receptor (RXR) α-dependent gel shift assay. Studies with mutant receptors suggest that T0070907 modulates the interaction of PPARγ with these cofactor proteins by affecting the conformation of helix 12 of the PPARγ ligand-binding domain. Interestingly, whereas the T0070907-induced NCoR recruitment to PPARγ/RXRα heterodimer can be almost completely reversed by the simultaneous treatment with RXRα agonist LGD1069, T0070907 treatment has only modest effects on LGD1069-induced coactivator recruitment to the PPARγ/RXRα heterodimer. [1] T0070907 treatment inhibits proliferation, invasion and migration but does not significantly affect apoptosis. Molecular inhibition using a dominant negative (Δ462) receptor yields similar results. T007 also mediates a dose-dependent decrease in phosphorylation of PPARγ, and its ability to bind to DNA, and may directly affect mitogen-activated protein kinase signaling. [2] |
in vivo | Lipopolysaccharide preconditioning significantly attenuates the development of renal dysfunction, hepatocellular injury, and circulatory failure as well as the increase in the plasma levels of interleukin-1 [beta] caused by severe endotoxemia. T0070907 can attenuate all of these beneficial effects afforded by preconditioning with lipopolysaccharide [3] |
キナーゼアッセイ | Ligand Binding Assay | |
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To determine the binding affinity of T0070907 to the PPARs, scintillation proximity assay (SPA) is performed with the following modifications. A 90-μl reaction contains SPA buffer (10 mm KH2PO4, 10 mm KH2PO4, 2 mm EDTA, 50 mm NaCl, 1 mm dithiothreitol, 2 mmCHAPS, 10% (v/v) glycerol, pH 7.1), 50 ng of GST-PPARγ (or 150 ng of GST-PPARα, GST-PPARδ), 5 nm 3H-labeled radioligands, and 5 μl of T0070907 in Me2SO. After incubation for 1 h at room temperature, 10 μl of polylysine-coated SPA beads (at 20 mg/ml in SPA buffer) are added, and the mixtureis incubated for 1 h before reading in Packard Topcount. [3H]Rosiglitazone is used for PPARγ, and [3H]GW2433 is used for PPARα and PPARδ. | ||
細胞アッセイ | 細胞株 | MCF-7 cells |
濃度 | 20 μM and higher concentrations | |
反応時間 | 48 h | |
実験の流れ | MTS assay |
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動物実験 | 動物モデル | Preconditioning is performed by administering a low dose (1 mg/kg) of Escherichia coli LPS (serotype 0.127:B8) intraperitoneally 24 hr before the induction of severe endotoxemia. |
投薬量 | 1 mg/kg | |
投与方法 | intraperitoneally |
Data from [Data independently produced by , , Aging Cell, 2018, doi: 10.1111/acel.12774]
Data from [Data independently produced by , , Int Immunopharmacol, 2015, 26(1): 58-64]
Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence [ Nat Commun, 2024, 15(1):1429] | PubMed: 38365899 |
PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy [ Cell Discov, 2023, 9(1):54] | PubMed: 37291146 |
PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy [ Cell Discov, 2023, 9(1):54] | PubMed: 37291146 |
PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARγ [ Diabetes, 2023, 72(8):1095-1111] | PubMed: 37216643 |
PRMT4 Facilitates White Adipose Tissue Browning and Thermogenesis by Methylating PPARγ [ Diabetes, 2023, 72(8):1095-1111] | PubMed: 37216643 |
Ganoderma lucidum polysaccharides attenuates pressure-overload-induced pathological cardiac hypertrophy [ Front Pharmacol, 2023, 14:1127123] | PubMed: 37033616 |
Ganoderma lucidum polysaccharides attenuates pressure-overload-induced pathological cardiac hypertrophy [ Front Pharmacol, 2023, 14:1127123] | PubMed: 37033616 |
Telmisartan inhibits microglia-induced neurotoxic A1 astrocyte conversion via PPARγ-mediated NF-κB/p65 degradation [ Int Immunopharmacol, 2023, 123:110761] | PubMed: 37544025 |
α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously [ Drug Des Devel Ther, 2023, 17:563-577] | PubMed: 36860800 |
The downstream PPARγ target LRRC1 participates in early stage adipocytic differentiation [ Mol Cell Biochem, 2023, 478(7):1465-1473] | PubMed: 36370237 |
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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