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Purity: ≥98%
Tropifexor (also known as LJN452) is a novel, potent and highly potent agonist of FXR (farnesoid X receptor) with an EC50 value of 0.2 nM in HTRF assay. It shows potent in vivo activity in rodent PD models by measuring the induction of FXR target genes in various tissues. It has the potential for the Treatment of Cholestatic Liver Diseases and Nonalcoholic Steatohepatitis (NASH). Tropifexor has advanced into phase 2 human clinical trials in patients with NASH and PBC. The farnesoid X receptor (FXR) is a nuclear receptor that acts as a master regulator of bile acid metabolism and signaling. Activation of FXR inhibits bile acid synthesis and increases bile acid conjugation, transport, and excretion, thereby protecting the liver from the harmful effects of bile accumulation, leading to considerable interest in FXR as a therapeutic target for the treatment of cholestasis and nonalcoholic steatohepatitis.
| ln Vitro |
Compound 1, tropifexor, is a novel FXR agonist with an EC50 of 0.2 nM that is very potent. In primary cells treated with Tropifexor, there was a concentration-dependent strong induction of the SHP and BSEP genes. Concentrations as low as 1 nM showed higher induction of BSEP than vehicle (DMSO) controls, whereas 3 times at 1 nM there was strong induction by SHP (15-fold higher than vehicle) and moderate induction by SHP [1].
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| ln Vivo |
Compound 1 (tropifexor) showed effective stimulation of FGF15 and SHP in the ileum at dosages as low as 0.1 mg/kg. Strong SHP induction was seen in the liver at 0.01 mg/kg Tropifexor, and gene induction peaked at 0.3 mg/kg. After 14 days of Tropifexor therapy, CYP8B1 mRNA expression was already noticeable at the lowest dose (0.003 mg/kg), but at doses greater than 0.03 mg/kg, CYP8B1 gene expression was totally repressed. The plasma levels of FGF15 protein in rats treated with Tropifexor increased significantly in a dose-dependent manner, reaching their peak levels seven hours after the drug was administered. After 14 days of treatment, there was a significant dose-dependent decrease in blood triglycerides with a maximum response dose of 0.3 mg/kg, which led to triglyceride levels that were almost 79% lower than vehicle controls [1].
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| References |
[1]. Tully DC, et al. 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 8
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| Molecular Formula |
C29H25F4N3O5S
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| Molecular Weight |
603.59
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| CAS # |
1383816-29-2
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| SMILES |
S1C2C=C(C(=O)O)C=C(C=2N=C1N1[C@@H]2CC(C[C@H]1CC2)OCC1C(C2C=CC=CC=2OC(F)(F)F)=NOC=1C1CC1)F
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6568 mL | 8.2838 mL | 16.5675 mL | |
| 5 mM | 0.3314 mL | 1.6568 mL | 3.3135 mL | |
| 10 mM | 0.1657 mL | 0.8284 mL | 1.6568 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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