TGR5 (GPCR19激动剂)

化学名

3-(2-chlorophenyl)-N-(4-chlorophenyl)-N,5-dimethyl-1,2-oxazole-4-carboxamide

简称

TGR5

别名

TGR5 Receptor Agonist, CCDC, AOB2659, BDBM50414954, ZINC43208218

中文名

N/A

化学式

C₁₈H₁₄Cl₂N₂O₂

分子量

361.22

CAS号

1197300-24-5

纯度

98%

溶剂/溶解度

Water<1mg/ml; DMSO40mg/ml; Ethanol40mg/ml

溶液配制

5mg加入1.38ml DMSO，或者每3.61mg加入1ml DMSO，配制成10mM溶液。SD2384-10mM用DMSO配制。

产品描述

TGR5 Receptor Agonist, a potent TGR5(GPCR19) agonist, showed improved potency in the U2-OS cell assay (pEC50=6.8) and in melanophore cells (pEC50=7.5).

信号通路

GPCR & G Protein

靶点

TGR5

－

－

－

－

IC50

－

－

－

－

－

体外研究

TGR5 Receptor Agonist was profiled against more than 100 in-house and external 7TM, ion channel, enzyme, transporter, and nuclear hormone receptor selectivity assays, including FXR, another bile acid receptor, and showed significant response only in secretion of the pro-inflammatory cytokine TNFalpha (pIC50=6.8) in human primary monocytes following stimulation with LPS (lipopolysaccharide). In addition, TGR5 Receptor Agonist has good physicochemical properties and no measurable activity against three of the common cytochrome P450 (CYP450) isoforms (1A2, 2C9, and 2D6) or hERG dofetilide binding (pIC50<4.3). In rat pharmacokinetic (PK) studies, however, TGR5 Receptor Agonist showed high in vivo clearance (Cl=85ml/min/kg) and intrinsic clearance (Clint=48ml/min/g) which provided a reasonable explanation for the observed poor exposure. Because the TGR5 receptor is expressed in the GI tract at levels that increase corresponding with L-cell population density, we believe that agonists such as 6 and 7 possessing poor systemic exposure are good tool compounds for directly targeting the TGR5 receptor in the GI tract via local administration (vide infra) rather than systemic exposure. Our hypothesis was that for this receptor, systemic exposure was not necessary to achieve the desired effect of stimulating GLP-1 secretion in vivo.

体内研究

N/A

临床实验

N/A

特征

N/A

酶活性检测实验

方法

N/A

细胞实验

细胞系

N/A

浓度

N/A

处理时间

N/A

方法

N/A

动物实验

动物模型

N/A

配制

N/A

剂量

N/A

给药方式

N/A

产品编号

产品名称

包装

SD2384-10mM

TGR5 (GPCR19激动剂)

10mM×0.2ml

SD2384-5mg

TGR5 (GPCR19激动剂)

5mg

SD2384-25mg

TGR5 (GPCR19激动剂)

25mg

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说明书

1份