Nidufexor is an orally available farnesoid X receptor (FXR) agonist with an EC50 value of 25nM[1]. Nidufexor is the effective EphA2 antagonist that prevents EphA2-ephrin-A1 interaction, with an IC50 value of 45µM[2]. Nidufexor has been widely used as a lead compound to optimize the structure by supplementing functional groups for the preparation of potent derivatives[3]. Nidufexor has been widely used to inhibit liver fat and improve liver function[4].
In vivo, Nidufexor treatment via oral administration at a dose of 30mg/kg daily for 4 weeks alleviated liver fibrosis in a mouse model of non-alcoholic fatty liver disease (NASH), reduced liver lipid accumulation and steatosis[5].
References:[1] Shi D Y, Shi X W, Shi H, et al. Discovery of novel potent indazole-based FXR agonists via scaffold hopping for MASH treatment[J]. European Journal of Medicinal Chemistry, 2025: 118203.
[2] Ferrari F R, Giorgio C, Zappia A, et al. Pharmacological characterization of second generation FXR agonists as effective EphA2 antagonists: A successful application of target hopping approach[J]. Biochemical Pharmacology, 2023, 209: 115452.
[3] Teno N, Gohda K, Fujimori K. A Review on Farnesoid X Receptor (FXR) Modulators Focusing on Benzimidazole Scaffold[J]. Molecules, 2026, 31(3): 450.
[4] Chen C, Zhou X, Cheng W, et al. Design, synthesis and FXR partial agonistic activity of anthranilic acid derivatives bearing aryloxy moiety as therapeutic agents for metabolic dysfunction-associated steatohepatitis[J]. Bioorganic Chemistry, 2024, 153: 107940.
[5] Chianelli D, Rucker P V, Roland J, et al. Nidufexor (LMB763), a novel FXR modulator for the treatment of nonalcoholic steatohepatitis[J]. Journal of medicinal chemistry, 2020, 63(8): 3868-3880.