T0070907

製品コードS2871 バッチS287107

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C12H8ClN3O3
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）
Clear solution
5%DMSO 45%PEG300 50%ddH2O
2.75mg/ml Taking the 1 mL working solution as an example, add 50 μL of 55 mg/ml clarified DMSO stock solution to 450 μL of PEG 300, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <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.

溶剤液（一定の濃度）を調合する

生物活性

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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ Ligand Binding Assay
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
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

カスタマーフィードバック

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]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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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