| 名称 | Zosuquidar trihydrochloride |
| 描述 | Zosuquidar trihydrochloride (LY-335979 trihydrochloride) is a highly selective, potent competitive inhibitor of P-glycoprotein (P-gp, ABCB1) with a Ki value of 59 nM. Zosuquidar trihydrochloride exhibits antitumor activity and can be used in research on tumors such as leukemia. |
| 细胞实验 | Cell viability is determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method. Cells are harvested during logarithmic growth phase, and seeded in 96-well plates. The cells are then cultured for 72 hours in the presence of oncolytics with or without modulators. MCF-7 and MCF-7/ADR cells are incubated 24 hours before the addition of the drug with and without the LY335979. LY335979 is prepared as 2 mM DMSO stocks and added to wells to give final concentrations ranging from 0.05 to 5 μM. After 72 hours, 20 μL of freshly prepared 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (5 mg/mL in Dulbecco's PBS) is added to each well and incubated for 4 hours in a 37 °C incubator containing 5% CO2. Cells are pelleted in a Sorvall RT6000B centrifuge, 70 μL of medium is carefully removed from each well, and 100 μL of 2-propanol/0.04 N HC1 is added. Cells are resuspended 5-10 times with a Multipipettor or until no particulate matter is visible. Plates are immediately read on a Titertek Multiskan MCC/340 microplate reader Flow Laboratories with a test wavelength of 570 nm and a reference wavelength of 630 nm. Controls are measured in quadruplicate and modulators are measured in duplicate. Cytotoxicity analyses are also performed using the CeliTiter 96 AQueous assay kit.(Only for Reference) |
| 激酶实验 | ATPase Assay : P-Glycoprotein ATPase activity is measured by the liberation of inorganic phosphate from ATP. The assay is measured in a 96-well plate for 90 min at 37 °C. Membranes (8 μg-10 μg protein) are incubated in a total volume of 100 μL of buffer A containing 5 mM sodium azide, 1 mM ouabain, 1 mM EGTA, 3 mM ATP, an ATP regenerating system composed of 5 mM phosphoenolpyruvate, and 3.6 units/mL pyruvate kinase in the presence and absence of 1 mM sodium vanadate. Pgp-ATPase activity is defined as the vanadate-sensitive portion of the total ATPase activity. Plates are read 3 minutes after the addition of the detection solution. The absorbance is measured at 690 nm by a microtiter dish reader. A phosphate standard curve is used to calculate the μMol of phosphate formed. Samples are measured in triplicate. |
| 体外活性 | 方法：在 P-gp 高表达的细胞系中加入 P-gp 抑制剂 Zosuquidar trihydrochloride （0.3 μM），同时加入 AVE9633 或 DM4 （3.125， 6.25， 12.5， 25， 50， 100 and 200 nM），AVE9633 处理 4 天，DM4 处理 3 天。单层细胞外排实验检测 P-gp 抑制。
结果：Zosuquidar trihydrochloride 完全恢复了 P-gp 表达细胞对 AVE9633 和 DM4 的敏感性。[1]
方法：从 High-Five 昆虫细胞制备的表达野生型或突变型 P-gp 的粗膜。将膜蛋白与不同浓度抑制剂（zosuquidar， elacridar， tariquidar，浓度范围 0-100 μM）在 37°C 孵育，加入 5 mM ATP 启动反应，20 分钟后 用 SDS 终止，通过比色法检测无机磷释放量。
结果：在野生型 P-gp 中，Zosuquidar trihydrochloride 等抑制剂浓度依赖性抑制基础 ATP 酶活性，IC₅₀在 10-30 nM 范围。[2] |
| 体内活性 | 方法：野生型小鼠通过颈动脉插管，以恒定流速(2.5 mL/min)向大脑灌注含有药物(imatinib， 0.05 - 50 μM; Zosuquidar trihydrochloride， 0.5 μM)的生理缓冲液。灌注结束后，立即处死小鼠，取脑组织测定药物浓度，计算脑摄取率。
结果：Zosuquidar trihydrochloride 使 imatinib 脑摄取增加 2.5 倍。[3] |
| 存储条件 | Keep away from moisture,Store under nitrogen,The compound is unstable in solution. Please use soon,
Powder: -20°C for 3 years
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+90% Saline : 8.08 mg/mL (12.68 mM), Solution.
DMSO : 80.83 mg/mL (126.89 mM), Sonication is recommended.
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| 关键字 | Zosuquidar Trihydrochloride | Zosuquidar (LY335979) | Zosuquidar | UCLA-P3.003VLB | UCLA-P3 | RS 33295-198 Trihydrochloride | RS 33295-198 (D06387) | RS 33295-198 | P-gp (P-glycoprotein) | P-gp | Pgp | P-glycoprotein | P388/ADR | P388 | Multidrug resistance protein 1 | MDR1 | MCF7/ADR | MCF7 | LY-335979 Trihydrochloride | LY335979 Trihydrochloride | LY-335979 | LY335979 | LY 335979 Trihydrochloride | LY 335979 | K562 | Inhibitor | inhibit | HL60 | Cluster of differentiation 243 | CEM/VLB100 | CD243 | CCRF-CEM | anti-tumor activity | AML | acute myelogenous leukemia | ABCB1 | 2780AD | 2780 |
| 相关产品 | Bisdemethoxycurcumin | Trifluoperazine dihydrochloride | Tariquidar | Cinchonine | Glibenclamide | Bifendate | Verapamil hydrochloride | Atazanavir | Polyoxyethylene stearate | Atazanavir sulfate | Encequidar mesylate | 1-piperoylpiperidine |
| 相关库 | 生物活性化合物库Plus |