| 名稱 | YM-58483 |
| 描述 | YM-58483 (BTP2) is a specific and effective inhibitor of CRAC channels and subsequent Ca2+ signals. |
| 細(xì)胞實驗 | Jurkat cells (1×107 cells/ml) were tested with varying concentration of compounds for 30 min at 37°C. The cells were stimulated with 1 μM ionomycin for 30 min at 37°C. After stimulation, the cells were centrifuged at 200×g for 2 min, and were solubilized in 100 μl of Triton X-100 lysis buffer. The cell lysate was centrifuged at 15,000×g for 20 min; the clarified lysate was subjected to SDS-PAGE; and NF-ATc2 was detected by Western blotting with anti-NF-ATc2 mAb. (Only for Reference) |
| 激酶實驗 | HCT-116 cells are washed with PBS and then homogenized with a 27-gauge syringe in binding buffer (10 mm Tris-HCl (pH 7.4), 50 mm KCl, 5 mm MgCl2, 1 mm EDTA, and 0.1 mm Na3VO4). The cell lysate is centrifuged at 13,000 rpm for 30 min at 4°C, and the supernatant is collected. The HCT-116 cell lysate supernatant is precleared by incubating with Dynabeads M-280 streptavidin for 30 min at 4°C and captured by magnet separation. The cleared supernatants are incubated with biotinyl-KRIBB11 compound. After overnight incubation at 4°C, proteins associated with the biotinyl-KRIBB11 compound are precipitated with Dynabeads M-280 streptavidin. Precipitated samples are separated by a magnet. Samples are washed with 1 mL of ishing buffer containing 50 mm HEPES (pH 7.5), 50 mm NaCl, 1 mm EDTA, 1 mm EGTA, 0.1% Tween 20, 10% (v/v) glycerol, 1 mm NaF, 0.1 mm Na3VO4, and protease inhibitor mixture tablets (1 tablet/10 mL). Samples are boiled in SDS-PAGE sample buffer, separated by 10% polyacrylamide gel, and immunoblotted with antibodies against HSF1, HSF2, HSP90, or CDK9. |
| 體外活性 | 在多種過敏性哮喘模型,如氣道高反應(yīng)、早期和晚期支氣管狹窄、抗原誘導(dǎo)的氣道嗜酸性粒細(xì)胞中,YM-58483均有抑制效果,在大鼠和豚鼠器官中還出現(xiàn)白三烯、IL-4水平的降低.在GVHD小鼠中,YM-58483還可抑制抗宿主CTL反應(yīng)、供體T細(xì)胞擴(kuò)張及IFN-γ的產(chǎn)生.YM-58483（30 mg/kg,p.o.）對小鼠的一般活動沒有明顯影響[1]. |
| 體內(nèi)活性 | 作為選擇性SOCE阻滯劑,YM-58483在Jurkat T細(xì)胞中抑制anti-CD3抗體所誘導(dǎo)的持續(xù)性鈣離子流入。它抑制CRAC、TRPC3和TRPC5通道、促進(jìn)TRPM4通道,抑制細(xì)胞因子的產(chǎn)生（IL-2, IL-4, IL-5, IFN-γ等）及T細(xì)胞的增殖。通過抑制NF-AT的激活,YM-58483可抑制MLR相關(guān)的脾細(xì)胞增殖[1]。YM-58483對IL-2的產(chǎn)生和NF-AT驅(qū)動的啟動子活性也有明顯的抑制作用,但不影響Jurkat細(xì)胞中AP-1驅(qū)動的啟動子活性[2]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 78 mg/mL (185.1 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 78 mg/mL (185.1 mM)
|
| 關(guān)鍵字 | inhibit | CRAC Channel | Ca2+ release-activated Ca2+ channels | YM58483 | Calcium release-activated channels | BTP 2 | YM-58483 | BTP-2 | Inhibitor |
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