化合物 TR14035|T5310|TargetMol

TR-14035
232271-19-1

￥407 1mg 起订

￥942 5mg 起订

￥1430 10mg 起订

上海更新日期：2024-12-12

TargetMol中国（陶术生物）

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联系人：邵小姐

手机：4008200310 拨打

邮箱：marketing@tsbiochem.com

产品详情:

中文名称：: 化合物 TR14035

英文名称：: TR-14035

CAS号：: 232271-19-1

品牌：: TargetMol

产地：: 美国

保存条件：: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice.

纯度规格：: 99.81%

产品类别：: 抑制剂

货号：: T5310

Product Introduction

Bioactivity

名称	TR-14035
描述	TR-14035 (MDK-1191) is a dual antagonist of α4β7/α4β1 integrins (IC50s: 7/87nM).
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].
体外活性	TR-14035（IC50：alpha(4)beta(7)/alpha(4)beta(1)=7/87 nM）已完成欧洲的第一阶段研究[1]。在大鼠和人类肝细胞中，TR-14035的摄取是通过一个明显的单一饱和机制进行的，其K(m)分别为6.7和2.1 microM，而牛磺胆酸和地高辛可以减少这种摄取。在卵母细胞中表达的OATP1B1/OATP-C 和 OATP1B3/OATP8介导了TR-14035的摄取，其K(m)分别为7.5和5.3 microM[2]。TR14035阻断了人类alpha(4)beta(7)与(125)I-MAdCAM-Ig融合蛋白的结合，IC(50)值为0.75 nM。在体外剪切流条件下，TR14035阻断了表达人类alpha(4)beta(7)的RPMI-8866细胞或小鼠肠系膜淋巴结淋巴细胞与MAdCAM-Ig的结合，IC(50)值为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]。
存储条件	Powder: -20°C for 3 years \| In solvent: -80°C for 1 year \| Shipping with blue ice.
溶解度	H2O : Insoluble DMSO : 40 mg/Ml (84.3 mM)
关键字	MDK1191 \| autoimmune \| TR-14035 \| disease \| asthma \| Integrin \| inhibit \| MDK 1191 \| TR 14035 \| allergic \| TR14035 \| inflammation \| Inhibitor \| alpha(4)
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MDK-1191|TargetMol

TargetMol Chemicals Inc. 总部位于马萨诸塞州波士顿，致力于为全球生化领域科学家的研究提供专业的产品和服务。TargetMol?品牌的客户群分布于40多个国家和地区，已发展成为全球知名的化合物库和小分子化合物研究供应商。 TargetMol?可提供160多种满足不同需求的化合物库，以及多种类型的生化试剂产品，包括12000多种抑制剂、16000多种天然产物和各类多肽、抗体、生命科学试剂盒等，此外，我们还建设有CADD（计算机辅助药物设计）研究中心、药理实验室、药化合成平台三大技术中心，全方位满足客户的定制需求。凭借我们优质的产品和服务、快速高效的全球供应链和专业的技术支持，我们将有效帮助您缩短研发周期，取得更成功的结果。

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