Tropifexor

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Tropifexor (LJN-452, LJN452) 是一种新型高效、选择性、口服活性 FXR 完全激动剂，EC50 为 0.26 nM。

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). (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.

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LJN-452 | LJN452

Metabolic Enzyme/Protease

FXR

FXR

Other Indications

Steatohepatitis

1383816-29-2

603.589

C29H25F4N3O5S

>98% (HPLC)

10 mM in DMSO

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

2-[(1R,3r,5S)-3-({5-cyclopropyl-3-[2-(trifluoromethoxy)phenyl]-1,2-oxazol-4-yl}methoxy)-8-azabicyclo[3.2.1]octan-8-yl]-4-fluoro-1,3-benzothiazole-6-carboxylic acid

(-20℃)

With Ice Pack

≥ 2 years