| 名稱(chēng) | Sitaxsentan sodium |
| 描述 | Sitaxsentan sodium (TBC11251 sodium salt) is a highly selective antagonist of endothelin A receptors. |
| 細(xì)胞實(shí)驗(yàn) | TE 671 or transfected COS 7 cells are grown to confluence in six-well plates. Sixteen hours prior to use, the media in each well is replaced with 2 mL of inositol-free RPMI-164 (IF-RPMI) media containing 10% inositol-free FCS and 2 mCi [3H]myoinositol and incubated at 37 °C in the presence of 6% CO2. The media is aspirated, and the cells are washed twice with PBS. Cells are preincubated for 10 minutes in 1 mL of lithium buffer (15 μM HEPES, pH 7.4, 145 μM NaCl, 5.4 μM KCl, 1.8 μM CaCl2, 0.8 μM MgSO4, 1.0 μM NaH2PO4, 11.2 μM glucose, 20 μM LiCl) with or without Sitaxentan sodium prior to the addition of 100 μM of ET-1 at different concentrations. Cells are then incubated for an additional 45 minutes. The buffer is discarded, and the accumulated inositol phosphates are extracted with ice cold methanol. The total cell protein in each well is measured using the BCA assay after solubilizing the cells in 0.1 M NaOH.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Ligand binding studies: Binding studies are performed in a 30 mM HEPES buffer, pH 7.4, containing 150 mM NaCl, 5 mM MgCl2, and 0.05% bacitracin using 2 mg/tube (ETA) or 0.75 mg/tube (ETB) membrane. Sitaxentan sodium is dissolved in DMSO and diluted with the assay buffer to give a final concentration of 0.25% DMSO. Competitive inhibition experiments are performed in triplicate in a final volume of 200 μL containing 4 pM [125I]ET-1 (1.6 nCi). Nonspecific binding is determined in the presence of 100 nM ET-1. Samples are incubated for 16 hours?18 hours at 24 °C. One milliliter of PBS is then added and the assay centrifuged at 2000 g for 25 minutes at 4 °C. The supernatant is decanted and the membrane bound radioactivity counted on a Genesys gamma counter. |
| 動(dòng)物實(shí)驗(yàn) | Sitaxsentan is formulated in water.After an initial 2-week period of hypoxic exposure (10% O2) sitaxsentan (15 or 30 mg/kg body weight per day in the drinking water) is administered for 4 weeks during continuous exposure to hypoxia. At the conclusion of the 4 week period of hypoxia, femoral and pulmonary arterial cannulation and measurement of MPAP, MSAP, and HR are performed. |
| 體外活性 | Sitaxsentan（低氧發(fā)作前10分鐘注射5 mg/kg）完全阻斷低氧誘導(dǎo)的血管收縮,并且該組與空氣對(duì)照沒(méi)有差異.Sitaxsentan的口服給藥顯著減弱MPAP的增加,而對(duì)暴露于正常氧氣水平的大鼠施用Sitaxsentan不會(huì)影響MPAP.單獨(dú)使用Sitaxsentan可以限制分流引起的MT增加. |
| 體內(nèi)活性 | Sitaxsentan和Bosentan在較高濃度下減弱NTCP轉(zhuǎn)運(yùn),并抑制人肝轉(zhuǎn)運(yùn)蛋白,這為在臨床環(huán)境中觀察到的這些藥物增加肝毒性提供了潛在的機(jī)制。Sitaxsentan及Sitaxsentan聯(lián)合西地那非可以完全阻止內(nèi)皮素-1和ETB受體的表達(dá)增加。單獨(dú)使用Sitaxsentan部分恢復(fù)了BMPR-1A和BMPR-2的表達(dá)。西地那非和Sitaxsentan聯(lián)用進(jìn)一步恢復(fù)了BMPR-1A和BMPR-2的表達(dá),然而,與對(duì)照相比仍然是降低的水平。 |
| 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 : 60 mg/mL (125.82 mM)
Ethanol : 20 mg/mL (41.93 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | IPI1040 | TBC-11251 | Inhibitor | IPI-1040 | Sitaxsentan sodium | Sitaxsentan | inhibit | TBC 11251 | TBC11251 sodium | Endothelin Receptor | IPI 1040 |
| 相關(guān)產(chǎn)品 | Clazosentan | Aprocitentan | Edonentan | Sparsentan | Sulfisoxazole | Macitentan | BMS 182874 | BMS 182874 hydrochloride | Ambrisentan | Bosentan |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 已知活性化合物庫(kù) | ReFRAME 相關(guān)化合物庫(kù) | 神經(jīng)遞質(zhì)受體化合物庫(kù) | 抗心血管疾病化合物庫(kù) | GPCR靶點(diǎn)分子庫(kù) | 膜蛋白靶向化合物庫(kù) | 藥物功能重定位化合物庫(kù) | 疼痛相關(guān)化合物庫(kù) |