| 名稱 | RS-127445 |
| 描述 | RS-127445 (MT500) is a selective 5-HT2B receptor antagonist with pKi of 9.5 and pIC50 of 10.4, exhibits >1000-fold selectivity against other 5-HT receptors. |
| 細(xì)胞實驗 | RS-127445, vehicle or other antagonists are pre-incubated with 240 μl of HEK-293 cells expressing the human 5-HT2B receptor suspension at 37 °C for 20 min. HEK-293 cells are incubated with[3H]-myoinositol (1.67 μCi/ml) in 162 cm2 flasks overnight at 37 °C in an inositol free Ham's F12 medium containing 10% dialyzed foetal bovine serum. The cells are harvested, washed five times with phosphate bufffered saline and resuspended in inositol free Ham's F12 media at density of approximately 3×103 cells/ml. The reactions are initiated by addition of 5-HT. Sixty minutes later, the reactions are terminated by adding 50 μl of ice-cold 20% perchloric acid, chilled in an ice-water bath for 10 min and then neutralized with 160μl of 1 N KOH. Each sample is diluted with 2 ml of 50 mM Tris-HCl, pH 7.4 at room temperature. The aqueous portion (2.2 ml) is transferred onto Dowex AG1X8 columns (1 ml, 1 : 1, w/v) which has been washed with 5 ml of distilled water. The columns are then washed with 18 ml of distilled water and the inositol phosphates are eluted with 3 ml of 1 N HCl. The eluted radioactivity is determined by liquid scintillation spectroscopy using a Packard 1900CA analyzer. [1] (Only for Reference) |
| 激酶實驗 | Radioligand binding: The selectivity of RS-127445 for 5-HT2B receptors is examined by testing the compound for affinity at over 100 additional ion channel or receptor binding sites. CHO-K1 cells expressing human 5-HT2A, 5-HT2B or 5-HT2C receptors are harvested using 2 mM EDTA in phosphate buffered saline. Cell membranes are prepared by four cycles of homogenization and centrifugation (48,000×g for 15 min). Each assay is established so as to achieve steady state conditions and to optimize specific binding. For the 5-HT2A receptor, membranes from 1×106 cells are incubated with 0.2 nM [3 H]-ketanserin at 32 °C for 60 min. Nonspecific binding is determined using 10 μM methysergide. For the 5-HT2B receptor, membranes from 1.5×106 cells are incubated with 0.2 nM [3 H]-5-HT at 48 °C for 120 min. Nonspecific binding is determined using 10 μM 5-HT. For the 5-HT2Creceptor, membranes from 3×10 5 cells are incubated with 0.5 nM [3 H]-mesuler -gine at 32 °C for 60 min. Nonspecific binding is determined using 10 μM methysergide. Assays are terminated by vacuum filtration through glass fibre filters(GF/B) which has been pretreated with 0.1% polyethyleneimine. Total and bound radioactivity is determined by liquid scintillation counting. Greater than 90% specific binding is achieved in each of these assays. |
| 體外活性 | RS-127445是一種新型高親和力、選擇性5-HT2B受體拮抗劑，沒有可檢測的固有活性。RS-127445對5-HT2B受體的親和力達到nM級別，具有1000倍的選擇性。RS-127445能強效阻斷5-HT引起的肌醇磷酸生成增加，并以比約漢賓高1000倍的效能阻斷5-HT引起的細(xì)胞內(nèi)鈣濃度增加。[1] |
| 體內(nèi)活性 | RS-127445經(jīng)口服和腹膜內(nèi)給藥后迅速吸收，不受劑量或給藥方式限制，血漿濃度在給藥后15分鐘內(nèi)達到峰值。血漿中RS-127445的濃度與給藥劑量成正比。5 mg/kg劑量下，RS-127445的生物利用度約為腹膜內(nèi)給藥的60%和口服的14%。預(yù)計，RS-127445在血漿中的濃度足以完全飽和大鼠可接觸的5-HT2B受體，并可維持該狀態(tài)?？诜?到10 mg/kg的RS-127445能顯著抑制由束縛應(yīng)激引起的內(nèi)臟過敏性，抑制率達35%至74%?？诜S-127445能顯著抑制TNBS誘導(dǎo)的內(nèi)臟過敏性（3到30 mg/kg時的抑制率為15%到62%）?？诜?到30 mg/kg的RS-127445還能劑量依賴性地減少原生及TNBS處理的大鼠由束縛應(yīng)激引起的排便。[2]。RS-127445抑制結(jié)腸運動和排便。[3] |
| 存儲條件 | Keep away from moisture,
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+90% Saline : < 10 mg/mL (35.55 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
Ethanol : 8 mg/mL (28.44 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 10 mg/mL (35.55 mM), Suspension.
DMSO : 125 mg/mL (444.32 mM), Sonication is recommended.
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Serotonin Receptor | RS-127445 | RS127445 | RS 127445 | MT-500 | MT 500 | Inhibitor | inhibit | 5-hydroxytryptamine Receptor | 5HTReceptor | 5-HT2B | 5-HT Receptor | 5HT Receptor |
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