• 产品描述： Tropifexor is a novel and highly potent agonist of FXR with an EC50 of 0.2 nM.

• 靶点： Autophagy;FXR;FXR; Autophagy

• 体内研究：
  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.

• 参考文献：
  1. Tully DC,etal.Discovery of Tropifexor (LJN452), a Highly Potent Non-bile Acid FXR Agonist for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH).J Med Chem. 2017 Dec 28;60(24):9960-9973.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	1.657 ml	8.284 ml	16.568 ml
  5 mM	0.331 ml	1.657 ml	3.314 ml
  10 mM	0.166 ml	0.828 ml	1.657 ml
  50 mM	0.033 ml	0.166 ml	0.331 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *