预约演示
更新于：2026-08-31
Tropifexor
更新于：2026-08-31
概要
基本信息
药物类型 小分子化药 |
别名 Tropifexor (USAN)、LJN-452、NVP-LJN452-NXA |
靶点 |
作用方式 激动剂 |
作用机制 FXR激动剂(胆汁酸受体FXR激动剂) |
在研适应症- |
非在研适应症 |
在研机构- |
最高研发阶段终止临床2期 |
首次获批日期- |
最高研发阶段(中国)终止 |
特殊审评- |
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结构/序列
分子式C29H25F4N3O5S |
InChIKeyVYLOOGHLKSNNEK-PIIMJCKOSA-N |
CAS号1383816-29-2 |
关联
8
项与 Tropifexor 相关的临床试验NCT04147195
NASH EXploratory Single and COmbination Treatment (NEXSCOT): An Open Label, Multicenter, Platform Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Various Single and Combination Treatments in Patients With Non-alcoholic Fatty Liver Disease (NAFLD) Who Manifest a Non-alcoholic Steatohepatitis (NASH)-Like Biomarker Phenotype
NCT04408937
A Randomized, Investigator and Subject Blinded, Multicenter, Parallel-arm Study to Determine the Safety and Tolerability of Tropifexor.
NCT04065841
A Randomized, Double-blind, Parallel-group, Multicenter Study to Assess Efficacy, Safety, and Tolerability of Oral Tropifexor (LJN452) & Licogliflozin (LIK066) Combination Therapy and Each Monotherapy, Compared With Placebo for Treatment of Adult Patients With Nonalcoholic Steatohepatitis (NASH) and Liver Fibrosis.(ELIVATE)
100 项与 Tropifexor 相关的临床结果
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100 项与 Tropifexor 相关的转化医学
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100 项与 Tropifexor 相关的专利（医药）
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59
项与 Tropifexor 相关的文献（医药）2026-08-01CANCER LETTERS
Bile acid retention impairs tumoral antigen presentation and intrinsic tumor suppression in MASH-HCC
Article
作者: Wang, Jiabei ; Wei, Wei ; Ma, Jinhu ; Sun, Linmao ; Liu, Yufeng ; Zhao, Xueping ; Deng, Shumin ; Duan, Jiawei ; Zhang, Zhongyuan
Metabolic reprogramming enables tumor cells to evade immune surveillance, yet the mechanisms linking specific metabolic alterations to immune evasion remain incompletely understood. We found that in metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) cells, aberrant accumulation of bile acids impairs the NOD-like receptor family CARD domain containing 5-mediated major histocompatibility complex class I antigen presentation pathway, thereby leading to loss of antigenicity in tumor cells. Bile acid retention in tumor cells results primarily from the downregulation of the efflux pump ABCB11, driven by G protein-coupled receptor 120-mediated FXR suppression under lipid-rich conditions. Furthermore, genetic inactivation of NLRC5 abolishes the recovery of MHC-I expression and antitumor immunity upon bile acid reduction. Treatment with Tropifexor, a potent selective FXR agonist, synergizes with immune checkpoint blockade, significantly reducing tumor burden and potentiating the intratumoral adaptive immune response in mice. Thus, we reveal that intracellular bile acid accumulation suppresses both tumor antigenicity and intrinsic antitumor immunity. This insight provides a therapeutic target for improving immunotherapy outcomes in MASH-HCC.
2026-06-01JOURNAL OF MOLECULAR GRAPHICS & MODELLING
Decoding structural and dynamic determinants of Tropifexor-FXR binding: A comprehensive computational analysis
Article
作者: Kumar, Ram ; Sinha, Suman
Farnesoid X receptor (FXR) is a nuclear receptor considered a prominent therapeutic target associated with diseases such as non-alcoholic fatty liver disease, diabetes, and atherosclerosis. Tropifexor is a selective FXR agonist that shows promising activity against cholestatic liver diseases and non-alcoholic steatohepatitis. In this work, we performed comprehensive structural analyses and unbinding studies to investigate Tropifexor behaviour within the ligand binding domain using molecular dynamics (MD) simulations. Multiple repeats of 2 μs unbiased MD and WT-Metadynamics of the FXR-Tropifexor complex revealed salient aspects about ligand-induced agonism. Our analyses revealed that Tropifexor achieves its high FXR binding affinity and selectivity by simultaneously optimizing multiple interaction modes, including π-sulphur, π-π, and carbon-π contacts, which act as additional selectivity filters beyond conventional hydrogen bonding. The binding pocket volume expansion coupled with inter-helical distances fluctuations suggested a conformational wedge mechanism that stabilizes and activates the receptor through cooperative helical framework expansion. Furthermore, unbinding analyses revealed two distinct pathways. The most probable unbinding pathway (80% probability) embodies deep energy minima and significant dissociation barriers, which promote prolonged FXR receptor activation. The structural features elucidated in the current work serve as a rational blueprint for the discovery of next-generation FXR modulators with enhanced therapeutic indices.
2026-04-01Liver International
An Update on Bile Acid‐Regulated Signalling in the Pathogenesis of Metabolic Dysfunction‐Associated Steatotic Liver Disease
Review
作者: Wang, Li ; Wen, Yi ; Wang, Lu ; Wang, Hong‐Lian ; Chen, Chen ; Zhao, Chang‐Ying ; Shi, Jiang‐Shan ; Wu, Li‐Juan
ABSTRACT:
Metabolic dysfunction‐associated steatotic liver disease (MASLD) is a common metabolic disorder with rising global incidence without effective treatment. Emerging evidence highlights bile acids (BAs) as pivotal signalling molecules that modulate genes involved in their own metabolism and lipid homeostasis in hepatic and extrahepatic tissues, thereby influencing MASLD pathogenesis. These regulatory effects are primarily driven by the activation of nuclear receptors, including the farnesoid X receptor (FXR), vitamin D receptor (VDR), pregnane X receptor (PXR), and by the membrane‐bound G protein‐coupled receptors such as Takeda G protein‐coupled receptor 5 (TGR5) and sphingosine‐1‐phosphate receptor 2 (S1PR2). The distinct roles of these BA receptor‐dependent signalling pathways in lipid homeostasis underscore their importance in MASLD development. Pharmacological strategies targeting BA‐regulated pathways, particularly the FXR activation, have shown promise in MASLD treatment. Several FXR agonists, including obeticholic acid (OCA), cilofexor, and tropifexor, have progressed to clinical trials, demonstrating potential therapeutic efficacy. Additionally, recent studies identified several natural compounds—such as hyperoside, kaempferol, and salidroside—that exhibited direct or indirect FXR‐modulating properties, suggesting their potential utility for novel anti‐MASLD drug development. Further research into BA signalling mechanisms and the exploration of targeted therapies may provide novel and effective MASLD therapy.
62
项与 Tropifexor 相关的新闻（医药）2026-08-05
100 项与 Tropifexor 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
|---|---|---|---|
| D11548 | Tropifexor | - |
研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 肝纤维化 | 临床2期 | 美国 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 阿根廷 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 比利时 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 加拿大 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 捷克 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 埃及 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 法国 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 德国 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 印度 | 2018-09-11 | |
| 肝纤维化 | 临床2期 | 以色列 | 2018-09-11 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 350 | 窪獵製簾積選獵構鬱網(醖襯淵廠醖顧鑰醖醖廠) = 願廠製願範餘憲壓構遞 淵築鹹遞網糧鑰糧鹽膚 (構遞齋鏇艱襯鹽製鹽襯 ) 更多 | - | 2023-02-16 | |||
Placebo | 窪獵製簾積選獵構鬱網(醖襯淵廠醖顧鑰醖醖廠) = 網獵廠選餘獵範廠夢廠 淵築鹹遞網糧鑰糧鹽膚 (構遞齋鏇艱襯鹽製鹽襯 ) 更多 | ||||||
临床2期 | 61 | 選範選廠範願願衊衊廠(願築餘餘築醖廠窪鏇蓋) = 獵壓網範鹽顧醖膚憲糧 夢糧憲淵餘壓壓廠蓋衊 (鬱艱窪築積構艱壓鹹簾 ) 更多 | 积极 | 2022-07-21 | |||
Placebo | 選範選廠範願願衊衊廠(醖繭繭夢夢餘顧繭蓋醖) = 鬱壓鑰簾蓋遞鏇選襯選 觸獵襯構簾衊窪簾鹽憲 (築蓋顧鹽膚顧淵鏇膚齋 ) | ||||||
临床2期 | 20 | 餘範顧淵艱鏇糧範襯鹽(範鏇簾壓淵鑰製艱衊鹹) = 蓋淵顧顧廠壓窪簾遞鹹 願獵餘膚淵糧艱鹹夢廠 (襯鏇簾襯獵憲膚觸齋壓 ) | 积极 | 2020-09-01 | |||
Placebo | 餘範顧淵艱鏇糧範襯鹽(範鏇簾壓淵鑰製艱衊鹹) = 廠選遞廠遞獵餘膚齋鬱 願獵餘膚淵糧艱鹹夢廠 (襯鏇簾襯獵憲膚觸齋壓 ) | ||||||
临床2期 | 20 | (LJN452 ALL Patients) | 構觸選願餘壓糧範簾蓋 = 廠壓構廠顧選壓壓糧衊 鑰網範衊網壓網鏇鹹膚 (鹹衊遞憲壓齋築製願選, 簾鏇積鹹遞壓壓鏇襯夢 ~ 壓衊衊鏇繭廠構製襯壓) 更多 | - | 2019-05-01 | ||
Placebo (Placebo ALL Patients) | 構觸選願餘壓糧範簾蓋 = 築艱憲糧鏇繭廠製夢願 鑰網範衊網壓網鏇鹹膚 (鹹衊遞憲壓齋築製願選, 遞簾選窪廠積糧鬱願窪 ~ 製淵築築餘憲艱鑰廠網) 更多 | ||||||
临床2期 | 42 | 願獵膚襯網齋鑰積網範(範製遞醖窪選鬱衊願獵) = 選獵膚遞醖顧構積廠蓋 願顧築顧範網鑰壓簾蓋 (鏇築糧鹽襯構範衊壓衊 ) | - | 2019-01-03 |
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