Powder: -20°C for 3 years | In solvent: -80°C for 1 year
TR-14035 (MDK-1191) 是一种具有口服活性的 α4β7/α4β1整合素双重抑制剂,对 α4β7和 α4β1作用的 IC50值分别为 7 和 87 nM,可用于炎症和自体免疫疾病的研究。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 679 | 现货 | ||
2 mg | ¥ 981 | 现货 | ||
5 mg | ¥ 1,570 | 现货 | ||
10 mg | ¥ 2,390 | 现货 | ||
25 mg | ¥ 3,970 | 现货 | ||
50 mg | ¥ 5,680 | 现货 | ||
100 mg | ¥ 7,930 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 1,630 | 现货 |
产品描述 | TR-14035 (MDK-1191) is a dual antagonist of α4β7/α4β1 integrins (IC50s: 7/87nM). |
靶点活性 | α4β7 integrin:7 nM, α4β1 integrin:87 nM |
体外活性 | TR-14035 (IC50: alpha(4)beta(7)/alpha(4)beta(1)=7/87 nM) has completed Phase I studies in Europe [1]. TR-14035 was taken up by rat and human hepatocytes by an apparently single saturable mechanism with K(m) of 6.7 and 2.1 microM, respectively, and taurocholate and digoxin reduced this uptake. OATP1B1/OATP-C and OATP1B3/OATP8 expressed in oocytes mediated the TR-14035 uptake with K(m) of 7.5 and 5.3 microM, respectively [2]. TR14035 blocked the binding of human alpha(4)beta(7) to a (125)I-MAdCAM-Ig fusion protein with IC(50) values of 0.75 nM. Under shear flow in vitro, TR14035 blocked binding of human alpha(4)beta(7)-expressing RPMI-8866 cells or murine mesenteric lymph node lymphocytes to MAdCAM-Ig with IC(50) values of 0.1 microM [3]. |
体内活性 | 在EHBRs中,未变化的TR-14035的胆汁排泄和全身清除率显著低于正常大鼠,而在野生型与mdr1a/b-或Bcrp基因敲除小鼠之间,清除率无显著差异[2]。TR14035阻断了对HEVs的粘附(ED50:0.01-0.1 mpk i.v.)[3]。 |
细胞实验 | RPMI8866 cell line and Jurkat T lymphoblastoid cell line were grown as a suspension culture in RPMI 1640 media, 10% FCS, 2 mM glutamine, 100 units/mL penicillin G, 100 mg/mL streptomycin sulfate at 37 °C and 5% CO2. Adhesion assays have been detailed elsewhere. Microtiter plates were coated with 20 mg/mL HSA for 2 h at room temperature, washed once with PBS and derivatized with 10 mg/mL SPDP for 1 h. After washing, CS-1 (or sCS-1) derived peptide solution (100 mL at 100 μg/mL) was added to the wells and allowed to crosslink to the plates overnight at 4 °C. Non-reacted sites were blocked with 100 mL of 1% OV in PBS for 1 h at 37 °C. RPMI8866 cells were suspended in Dulbecco's modified Eagle's medium with 0.25% OV at a density of 2.5 ×106/mL and incubated for ~1 h at 37 °C with varying concentrations of antagonists on peptide-coated plates. Following washing (EL404 plate washer), bound cells were quantified by measuring endogenous N-acetyl-hexosaminidase activity by reading the optical density at 405 nm using the enzyme substrate p-nitrophenol-N-acetyl-b-d-glucoseaminide. IC50 values were generated by nonlinear regression from titration curves of antagonists from seven doses and reported as the average of a minimum of two experiments. Since experimental variability was noted with respect to the IC50 of the internal standard [(1S - cis) - N - [(3 - carboxy - 2,2,3 - trimethylcyclopentyl)- carbonyl]-O-[(2,6-dichlorophenyl)methyl]-l-tyrosine] a normalization procedure was done using the global mean value [IC50=0.224±0.17 μM (N=19)] of the internal standard. For the Jurkat cell adhesion assay, OV was replaced with 0.25% HSA for both blocking and adhesion buffers. Standard error of the mean for the Jurkat cell adhesion assay was typically <10% for each experiment and no normalization was needed [1]. |
动物实验 | For biliary excretion studies in mice and rats, a cannula (polyethylene tube, SP8 for mice and SP10 for rats) was inserted into the bile duct of the anesthetized animal. In the rat, after complete recovery from diethyl ether anesthesia, TR-14035 was administered intravenously at a dose of 3 mg/ml/kg, and the bile, urine, and blood were collected at designated time intervals. In the mouse, TR-14035 was administered intravenously at a dose of 3 mg/4 ml/kg, and the bile and blood were collected at designated time intervals under pentobarbital anesthesia. Blood was centrifuged to separate plasma, and all the samples were stored at j20 -C until analysis by LC-MSD [2]. |
别名 | MDK-1191 |
分子量 | 474.33 |
分子式 | C24H21Cl2NO5 |
CAS No. | 232271-19-1 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
H2O: Insoluble
DMSO: 40 mg/Ml (84.3 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.1082 mL | 10.5412 mL | 21.0824 mL | 52.7059 mL |
5 mM | 0.4216 mL | 2.1082 mL | 4.2165 mL | 10.5412 mL | |
10 mM | 0.2108 mL | 1.0541 mL | 2.1082 mL | 5.2706 mL | |
20 mM | 0.1054 mL | 0.5271 mL | 1.0541 mL | 2.6353 mL | |
50 mM | 0.0422 mL | 0.2108 mL | 0.4216 mL | 1.0541 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
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