| Bioactivity | Tropifexor (LJN452) is a highly potent agonist of FXR with an EC50 of 0.2 nM[1]. | ||||||||||||
| Target | EC50: 0.2 nM (FXR) | ||||||||||||
| Invitro | Tropifexor (compound 1) is a novel and highly potent agonist of FXR with an EC50 of 0.2 nM. 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)[1]. | ||||||||||||
| In Vivo | 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.Treatment of rats with Tropifexor exhibits a clear dose-dependent increase in plasma FGF15 protein, with maximal levels of FGF15 detected at 7 h postdose.Treatment with Tropifexor for 14 days produces a robust dose-dependent reduction in serum triglycerides and reaches a maximal response with a 0.3 mg/kg dose, resulting in a decrease of triglyceride levels to approximately 79% below the vehicle control group[1]. | ||||||||||||
| Name | Tropifexor | ||||||||||||
| CAS | 1383816-29-2 | ||||||||||||
| Formula | C29H25F4N3O5S | ||||||||||||
| Molar Mass | 603.58 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
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| Reference | [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. |