FXR/LIFR modulators(Università degli Studi di Napoli Federico II)(FXR/LIFR modulators(Università degli Studi di Napoli Federico II))

概要

基本信息

药物类型

小分子化药

别名

Compound 3a(Università degli Studi di Napoli Federico II)

靶点

FXR x LIFR

作用机制

FXR激动剂(胆汁酸受体FXR激动剂)、LIFR抑制剂(LIF receptor subunit alpha inhibitors)

治疗领域

消化系统疾病其他疾病

在研适应症

肝纤维化

非在研适应症-

原研机构

Università degli Studi di Napoli Federico II

在研机构

Università degli Studi di Napoli Federico II

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C24H17Cl2NO4

InChIKeyFVJFATSNWFWEGK-UHFFFAOYSA-N

CAS号2409154-23-8

关联

100 项与 FXR/LIFR modulators(Università degli Studi di Napoli Federico II) 相关的临床结果

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100 项与 FXR/LIFR modulators(Università degli Studi di Napoli Federico II) 相关的转化医学

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100 项与 FXR/LIFR modulators(Università degli Studi di Napoli Federico II) 相关的专利（医药）

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1

项与 FXR/LIFR modulators(Università degli Studi di Napoli Federico II) 相关的文献（医药）

2024-10-24·Journal of Medicinal Chemistry

Design, Synthesis, and Pharmacological Evaluation of Dual FXR-LIFR Modulators for the Treatment of Liver Fibrosis

Article

作者: Bordoni, Martina ; Massa, Carmen ; Morretta, Elva ; Zampella, Angela ; Finamore, Claudia ; Catalanotti, Bruno ; Spinelli, Lucio ; Cassiano, Chiara ; Lupia, Antonio ; Biagioli, Michele ; Fiorillo, Bianca ; Monti, Maria Chiara ; Sepe, Valentina ; Fiorucci, Stefano ; Rapacciuolo, Pasquale ; Moraca, Federica ; Urbani, Ginevra ; Marchianò, Silvia ; Giorgio, Cristina Di

Although multiple approaches have been suggested, treating mild-to-severe fibrosis in the context of metabolic dysfunction associated with liver disease (MASLD) remains a challenging area in drug discovery. Pathogenesis of liver fibrosis is multifactorial, and pathogenic mechanisms are deeply intertwined; thus, it is well accepted that future treatment requires the development of multitarget modulators. Harnessing the 3,4,5-trisubstituted isoxazole scaffold, previously described as a key moiety in Farnesoid X receptor (FXR) agonism, herein we report the discovery of a novel class of hybrid molecules endowed with dual activity toward FXR and the leukemia inhibitory factor receptor (LIFR). Up to 27 new derivatives were designed and synthesized. The pharmacological characterization of this series resulted in the identification of 3a as a potent FXR agonist and LIFR antagonist with excellent ADME properties. In vitro and in vivo characterization identified compound 3a as the first-in-class hybrid LIFR inhibitor and FXR agonist that protects against the development of acute liver fibrosis and inflammation.

100 项与 FXR/LIFR modulators(Università degli Studi di Napoli Federico II) 相关的药物交易

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