| 名稱 | GW9662 |
| 描述 | GW9662 (TIMTEC-BB SBB006523) is a specific PPARγ antagonist (IC50: 3.3 nM, in a cell-free assay), with 100 to 1000-fold functional selectivity for PPARγ than PPARα/δ in cells. |
| 細(xì)胞實(shí)驗(yàn) | MDA-MB-231 cells are seeded at a density of 1 × 105 cells per 25 cm3 tissue culture flask. After 24 h (day 0), the growth medium is replaced with fresh medium containing rosiglitazone (50 μM), GW9662 (10 μM) or both together. Control flasks receives 0.1% DMSO. Cells are harvested on days 0, 3, 5, 7, 10 for each treatment condition by trypsinisation, stained using trypan blue, and the total and viable number of cells per flask calculates using a haemocytometer.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Binding assay: The human PPARα, PPARγ, and PPARδ ligand binding domains (LBDs) are expressed in E. coli as polyhistidine-tagged fusion proteins. Receptors are immobilized on SPA beads by addition of the desired receptor (15 nM) to a slurry of streptavidin-modifed SPA beads (0.5 mg/mL) in assay buffer. The mixture is allowed to equilibrate for at least 1 hour at room temperature, and the beads are pelleted by centrifugation at 1×103 g. The supernate is discarded, and the beads are resuspended in the original volume of fresh assay buffer with gentle mixing. The centrifugation/resuspension procedure is repeated, and the resulting slurry of receptor-coated beads is used immediately or stored at 4 ℃ for up to 1 week before use. [3H]GW2443 are used as radioligands for determination of competition binding to PPARα, PPARγ, and PPARδ, respectively. Unless otherwise indicated, the buffer used for all assays is 50 mM HEPES (pH 7), 50 mM NaCl, 5 mM CHAPS, 0.1 mg/mL BSA, and 10 mM DTT. For some experiments, the HEPES (pH 7) is replaced with 50 mM Tris (pH 8). |
| 體外活性 | GW9662抑制PPARγ激活,并抑制人乳腺癌腫瘤細(xì)胞系（MCF7, MDA-MB-468, MDA-MB-231）生長（IC50：20 -30 μM）。GW9662結(jié)合PPARγ上的Cys(285),其是三種PPAR中較保守的。在MDA-MB-231細(xì)胞中,Rosiglitazone（50 μM）與GW9662（10 μM）聯(lián)用7天后,其存活細(xì)胞數(shù)的減少程度具有統(tǒng)計(jì)學(xué)意義。在原代鼠骨髓和RAW264.7細(xì)胞中,PPARγ1配體對(duì)RANKL誘導(dǎo)的破骨細(xì)胞形成有抑制作用,而GW 9662（2 μM）可濃度依賴性地逆轉(zhuǎn)這些配體的抑制作用。在RAW264.7細(xì)胞中,GW 9662（1 μM）抑制NF-κB的RANKL激活。 在BMs中,GW 9662（2 μM）阻斷IL-4對(duì)破骨細(xì)胞形成的抑制。在甲狀腺眼病患者的原代前脂肪細(xì)胞中,GW9662（10 μM）對(duì)激素和激動(dòng)劑誘導(dǎo)的脂肪細(xì)胞分化有抑制作用。 |
| 體內(nèi)活性 | 大鼠經(jīng)脂多糖（1 mg/kg,i.p.）預(yù)處理,可明顯減弱腎損傷和功能障礙引起的所有缺血/再灌注損傷特征.而GW9662（1 mg/kg,i.p.）可阻斷脂多糖的保護(hù)作用. |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 45 mg/mL (162.64 mM), Sonication is recommended.
Ethanol : 6.9 mg/mL (25 mM)), Heating is recommended.
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| 關(guān)鍵字 | GW9662 | Peroxisome proliferator-activated receptors | PPAR | TIMTEC-BB SBB 006523 | TIMTEC-BB SBB-006523 | Inhibitor | inhibit | GW-9662 |
| 相關(guān)產(chǎn)品 | Icariin | Fisetin | Daidzein | PHYTOL | 5-Aminosalicylic Acid | Gemfibrozil | Fenofibrate | 2,3-Butanediol | Naringenin | BADGE |
| 相關(guān)庫 | 抑制劑庫 | 抗乳腺癌化合物庫 | 脂代謝化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | 活性脂質(zhì)化合物庫 | 代謝化合物庫 | 抗衰老化合物庫 | 抗高血壓化合物庫 | 神經(jīng)退行性疾病化合物庫 |