化學(xué)名

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

簡(jiǎn)稱

TGR5

別名

TGR5 Receptor Agonist, CCDC, AOB2659, BDBM50414954, ZINC43208218

中文名

N/A

化學(xué)式

C₁₈H₁₄Cl₂N₂O₂

分子量

361.22

CAS號(hào)

1197300-24-5

純度

98%

溶劑/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。

產(chǎn)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).

信號(hào)通路

GPCR & G Protein

靶點(diǎn)

TGR5

－

－

－

－

IC50

－

－

－

－

－

體外研究

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.

體內(nèi)研究

N/A

臨床實(shí)驗(yàn)

N/A

特征

N/A

酶活性檢測(cè)實(shí)驗(yàn)

方法

N/A

細(xì)胞實(shí)驗(yàn)

細(xì)胞系

N/A

濃度

N/A

處理時(shí)間

N/A

方法

N/A

動(dòng)物實(shí)驗(yàn)

動(dòng)物模型

N/A

配制

N/A

劑量

N/A

給藥方式

N/A

產(chǎn)品編號(hào)

產(chǎn)品名稱

包裝

SD2384-10mM

TGR5 (GPCR19激動(dòng)劑)

10mM×0.2ml

SD2384-5mg

TGR5 (GPCR19激動(dòng)劑)

5mg

SD2384-25mg

TGR5 (GPCR19激動(dòng)劑)

25mg

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說(shuō)明書

1份