| 名稱 | U-73122 |
| 描述 | U-73122 (U73122) , an effective PLC inhibitor, reduces agonist-induced Ca2+ increases in platelets and PMN. |
| 細(xì)胞實(shí)驗(yàn) | U-73122 is dissolved in DMSO. Agonist-induced production of IP3 in PMN is measured by use of the competitive radiobinding assy. PMN (2 x 106-107) in 0.2 mL of phosphate-buffered saline, pH 7.4 [NaC1 (138 mM), Na2HPO4 (8.1 mM), KH2PO4 (1.5 mM), KCI (2.7 mM), CaCl2 (1.0 mM), MgC12 (1.0 mM) and glucose (0.1%, w/v)] are incubated in conical polypropylene tubes at 37°C in a shaking water bath. U-73122 or U-73343 is added (in 1 μL of DMSO) 3 min before the addition of agonist, FMLP (0.1 μM) plus cytochalasin B (5 μg/mL). FMLP and cytochalasin B are added in 1 μL each of DMSO and ethanol, respectively. Appropriate vehicle controls are included in each experiment. PMN incubation mixtures are quenched with the addition of 0.07 mL of ice-cold TCA (20%, w/v) and a portion (0.2 mL) of the TCA extract is processed for the measurement of IP3 by competitive radiobinding as described above for platelets. |
| 激酶實(shí)驗(yàn) | PMNs (4×107/4 mL) are incubated with U-73122 according to protocols. The reactions are stopped with cold calcium-free PBS. The cells are centrifuged at 750 × g (4°C) and resuspended in 1 mL of Triton X-100-free extraction buffer (50 mM Tris, pH 7.5, 50 mM fimercaptoethanol, 2 mM EGTA, 1 mM phenylmethylsulfonyl fluoride and 4 μg/mL of leupeptin, soybean trypsin inhibitor and aprotinin), and then sonicated for 10- and 5-sec consecutive bursts at 20% output. The lysates are centrifuged at 240 × g (4°C) for 20 mm in a TL-100 ultracentrifuge with the supernatant designated as the cytosol fraction. The pellet is resuspended in 1% Triton-containing extraction buffer, sonicated, shaken for 30 mm at 4°C and centrifuged (240 × g for 20 mm at 4°C). The supernatant constitutes the extractable particulate fraction, and the pellet is sonicated in extraction buffer with Triton and constituted the nonextractable particulate fraction. |
| 體外活性 | 0.1 mg/ml U73122分別抑制狗體內(nèi)角叉菜膠誘導(dǎo)的74%淋巴細(xì)胞和65%巨噬細(xì)胞積累到皮下腔隙.30 mg/kg U73122（i.p.）阻斷角叉菜膠處理1小時(shí)和3小時(shí)后大鼠后爪65%和80%的水腫.其還完全抑制小鼠腹膜炎模型中脂多糖誘導(dǎo)的巨噬細(xì)胞和淋巴細(xì)胞浸潤(rùn),以及前列腺素E2(80%),并且也會(huì)抑制12-O-十四酰-佛波醇-13-乙酸鹽誘導(dǎo)的小鼠耳腫脹. |
| 體內(nèi)活性 | U-73122抑制膠原蛋白誘導(dǎo)的血栓素B的產(chǎn)生,膠原蛋白通過抑制受體耦合的花生四烯酸轉(zhuǎn)移產(chǎn)生誘導(dǎo)作用。U73122也會(huì)抑制FMLP誘導(dǎo)的人多形核中性白細(xì)胞聚合,以及相關(guān)的IP3和甘油二酯的產(chǎn)生。U73122明顯抑制各種激動(dòng)劑,包括凝血酶,膠原蛋白,ADP,花生四烯酸誘導(dǎo)的人血小板的聚集（IC50為1-5 μM）。凝血酶或者U-46619通過抑制被血小板可溶組分催化的磷脂酰[3H]肌糖和磷脂酰[3H]肌糖4,5-二磷酸的水解（Ki：9/40 μM）,誘導(dǎo)IP3的產(chǎn)生和隨后細(xì)胞溶質(zhì)中Ca2+的快速增加,10 μM U-73122會(huì)對(duì)其產(chǎn)生抑制。 |
| 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 : 5.63 mg/mL (12.11 mM), Sonication is recommended.
H2O : < 0.1 mg/mL (insoluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 1.25 mg/mL (2.69 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 關(guān)鍵字 | inhibit | Phospholipase | Inhibitor | U-73122 | Ferroptosis | Lipoxygenase | U 73122 | LOX |
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| 相關(guān)庫(kù) | 抑制劑庫(kù) | 脂代謝化合物庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | 細(xì)胞周期化合物庫(kù) | 代謝化合物庫(kù) | 細(xì)胞凋亡化合物庫(kù) | NO PAINS 化合物庫(kù) | 臨床前化合物庫(kù) | 抗肥胖化合物庫(kù) |