Tropifexor

SKU: orb1226396

Description

Tropifexor (LJN-452, LJN452) is a novel highly potent, selective, orally acitive FXR full agonist with EC50 of 0.26 nM; shows no significant off-target activity (>10,000-fold selectivity for FXR) in a panel of targets, including TGR5 (>10 uM); demonstratesin vivo activity in rodent PD models, and shows potential for treatment of cholestatic liver diseases and NASH. Steatohepatitis,Phase 2 Clinical(In Vitro):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).\n(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.

Key Properties

• CAS Number: 1383816-29-2
• MW: 603.589
• Purity: >98% (HPLC)
• Formula: C₂₉H₂₅F₄N₃O₅S
• SMILES: O=C(C1=CC(F)=C2N=C(N3[C@@]4([H])C[C@H](OCC5=C(C6CC6)ON=C5C7=CC=CC=C7OC(F)(F)F)C[C@]3([H])CC4)SC2=C1)O
• Target: FXR
• Solubility: 10 mM in DMSO

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

LJN-452 | LJN452

Quick Database Links

Gene Symbol

FXR