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Tropifexor
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Tropifexor图片
CAS NO:1383816-29-2
包装与价格:
包装价格(元)
1 mg电议
5 mg电议
10 mg电议
50 mg电议
100 mg电议
200 mg电议
1 mL*10 mM(in DMSO)电议

产品名称
LJN452
产品介绍
Tropifexor 是一种新型的高效 FXR 激动剂,EC50 为 0.2 nM。

产品描述

Tropifexor is a novel and highly potent agonist of FXR with an EC50 of 0.2 nM.

体外活性

Robust induction of both BSEP and SHP genes is observed in primary cells by Tropifexor in a concentration-dependent manner. BSEP induction above vehicle (DMSO) control is observed at concentrations as low as 1 nM, while strong induction of SHP (15-fold above vehicle) is observed at 10 nM and modest induction of SHP at 1 nM (3-fold).

体内活性

Treatment of rats with Tropifexor exhibits a clear increase in plasma FGF15 protein in a dose-dependent manner, with maximal levels of FGF15 detected at 7 h postdose. Treatment with Tropifexor for 14 days results in a robust dose-dependent reduction in serum triglycerides and reaches a maximal response with a 0.3 mg/kg dose, causing a decrease of triglyceride levels to approximately 79% below the vehicle control group. Tropifexor (compound 1) demonstrates highly potent induction of SHP and FGF15 in the ileum as doses as low as 0.1 mg/kg. In the liver, robust induction of SHP is observed at 0.01 mg/kg of Tropifexor with maximal levels of gene induction achieved at 0.3 mg/kg. Expression of CYP8B1 mRNA following 14 day treatment with Tropifexor is already apparent at the lowest dose (0.003 mg/kg), and CYP8B1 gene expression is fully repressed at doses above 0.03 mg/kg.

细胞实验

Primary rat hepatocytes are plated in 24 well plates and incubated with a 5 point dose response of Tropifexor (compound 1) for 24 hours. RNA is harvested from the cells using the RNeasy 96 kit. Quantitative PCR is performed. The fold change of the transcript over no stimulation is calculated using the ΔΔCt method, with DMSO (vehicle control) being no stimulation.

动物实验

Adult male wild-type Sprague-Dawley rats are used in this study. All animals are fasted for 3 hours before oral dosing with Tropifexor (compound 1) or with vehicle. Tropifexor is administered orally using a range of four doses (0.03, 0.1, 0.3, and 1.0 mg/kg) and compare directly to the vehicle control group (vehicle: 0.5% methylcellulose, 0.5% Tween 80, 99% water, suspension). Animals are sacrificed seven hours after dosing using CO2, liver, ileum and whole blood (in heparinized tubes) samples are collected for analysis.

Cas No.

1383816-29-2

分子式

C29H25F4N3O5S

分子量

603.59

别名

LJN452

储存和溶解度

DMSO:80 mg/mL(132.5 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years