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TR-14035

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Chemical Structure| 232271-19-1 同义名 : SB 683698;MDK-1191;QJ-2620
CAS号 : 232271-19-1
货号 : A234495
分子式 : C24H21Cl2NO5
纯度 : 99%+
分子量 : 474.333
MDL号 : MFCD09970400
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 40 mg/mL(84.33 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 The integrins α4β1 and α4β7 are heterodimeric cell surface proteins that regulate the physiologic and pathologic responses in inflammation and autoimmune diseases. TR-14035 is a dual antagonist of both α4β1 and α4β7 with IC50 values of 87 nM and 7 nM, respectively[5]. It blocks the binding of human α4β7 to an 125I-hMAd-CAM-Ig fusion protein with an IC50 value of 0.75 nM. In RPMI-8866 cells expressing human α4β7, TR-14035 at 1 μM blocked the adhesion of cells to MAdCAM-Ig by 100% with an IC50 value of 0.01 μM. In murine 47-expressing cells, TR-14035 at the dose of 1 μM inhibited the adhesion of cells to murine MAdCAM-Ig by 78% with an IC50 value of 0.1 μM. When tested for the ability to block the adhesion of murine MLN lymphocytes to Peyer’s patch HEVs under shear flow in vivo, intravenous administration of TR-14035 (10mpk) blocked the binding of MLN lymphocytes to Peyer’s patch HEVs by 95% when MLN lymphocytes were pretreated with 100 μM TR-14035 for 10min, and by 88% without the preincubation[6].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.11mL

0.42mL

0.21mL

10.54mL

2.11mL

1.05mL

21.08mL

4.22mL

2.11mL
参考文献

[1]Egger LA, Kidambi U, et al. Alpha(4)beta(7)/alpha(4)beta(1) dual integrin antagonists block alpha(4)beta(7)-dependent adhesion under shear flow. J Pharmacol Exp Ther. 2002 Jul;302(1):153-62.

[2]Sircar I, Gudmundsson KS, et al. Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: discovery of TR-14035, a dual alpha(4)beta(7)/alpha(4)beta(1) integrin antagonist. Bioorg Med Chem. 2002 Jun;10(6):2051-66.

[3]Cortijo J, Sanz MJ, et al. A small molecule, orally active, alpha4beta1/alpha4beta7 dual antagonist reduces leukocyte infiltration and airway hyper-responsiveness in an experimental model of allergic asthma in Brown Norway rats. Br J Pharmacol. 2006 Mar;147(6):661-70.

[4]Tsuda-Tsukimoto M, Ogasawara Y, et al. Pharmacokinetics and metabolism of TR-14035, a novel antagonist of a4ss1/a4ss7 integrin mediated cell adhesion, in rat and dog. Xenobiotica. 2005 Apr;35(4):373-89.

[5]Sircar I, Gudmundsson KS, Martin R, Liang J, Nomura S, Jayakumar H, Teegarden BR, Nowlin DM, Cardarelli PM, Mah JR, Connell S, Griffith RC, Lazarides E. Synthesis and SAR of N-benzoyl-L-biphenylalanine derivatives: discovery of TR-14035, a dual alpha(4)beta(7)/alpha(4)beta(1) integrin antagonist. Bioorg Med Chem. 2002 Jun;10(6):2051-66. doi: 10.1016/s0968-0896(02)00021-4. PMID: 11937364.

[6]Egger LA, Kidambi U, Cao J, Van Riper G, McCauley E, Mumford RA, Amo S, Lingham R, Lanza T, Lin LS, De Laszlo SE, Young DN, Kopka IE, Tong S, Pikounis B, Benson E, Warwood S, Bargatze RF, Hagmann WK, Schmidt JA, Detmers PA. Alpha(4)beta(7)/alpha(4)beta(1) dual integrin antagonists block alpha(4)beta(7)-dependent adhesion under shear flow. J Pharmacol Exp Ther. 2002 Jul;302(1):153-62. doi: 10.1124/jpet.302.1.153. Erratum in: J Pharmacol Exp Ther. 2003 May;305(2):796. PMID: 12065712.