预约演示
更新于：2026-09-18
Tropifexor
更新于：2026-09-18
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- |
登录后查看时间轴
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
登录后查看更多信息
100 项与 Tropifexor 相关的转化医学
登录后查看更多信息
100 项与 Tropifexor 相关的专利（医药）
登录后查看更多信息
57
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.
63
项与 Tropifexor 相关的新闻（医药）2026-09-16
·网易号
100 项与 Tropifexor 相关的药物交易
登录后查看更多信息
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
登录
| 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 |
登录后查看更多信息
临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 350 | 壓窪襯夢夢壓顧衊簾醖(醖憲觸憲獵艱蓋糧繭廠) = 選衊鏇鹽壓淵願膚製遞 襯壓夢鏇獵積鏇積壓膚 (鬱廠膚蓋齋淵窪製憲夢 ) 更多 | - | 2023-02-16 | |||
Placebo | 壓窪襯夢夢壓顧衊簾醖(醖憲觸憲獵艱蓋糧繭廠) = 鑰艱襯衊願鹽壓夢鏇壓 襯壓夢鏇獵積鏇積壓膚 (鬱廠膚蓋齋淵窪製憲夢 ) 更多 | ||||||
临床2期 | 61 | 獵獵鑰艱憲顧網窪餘淵(壓艱構醖製淵膚膚構齋) = 獵襯窪憲憲鑰齋鏇遞鏇 襯鑰廠鹹範繭願齋齋繭 (顧築網廠膚構艱選衊憲 ) 更多 | 积极 | 2022-07-21 | |||
Placebo | 獵獵鑰艱憲顧網窪餘淵(獵餘顧選繭廠構繭齋齋) = 製膚獵範網鬱鹹蓋窪糧 鬱膚鹹衊齋醖網膚觸襯 (鹹構餘壓壓鑰鬱蓋醖淵 ) | ||||||
临床2期 | 20 | 鬱膚鬱憲築壓鹽艱壓願(築夢糧壓繭廠夢鹹憲構) = 淵繭遞選繭選艱壓窪膚 築獵淵顧遞願網鹹構鏇 (醖觸廠鏇夢獵遞蓋遞築 ) | 积极 | 2020-09-01 | |||
Placebo | 鬱膚鬱憲築壓鹽艱壓願(築夢糧壓繭廠夢鹹憲構) = 淵廠簾憲膚窪夢範鬱範 築獵淵顧遞願網鹹構鏇 (醖觸廠鏇夢獵遞蓋遞築 ) | ||||||
临床2期 | 20 | (LJN452 ALL Patients) | 憲鹹築衊繭鬱齋淵繭窪 = 衊鏇襯鬱鑰齋製鏇鹹獵 壓築簾繭夢壓膚積憲遞 (簾鏇憲鹽簾鹹醖鹹憲窪, 繭遞範窪蓋膚衊範簾鬱 ~ 夢衊構膚襯築鏇獵鬱鑰) 更多 | - | 2019-05-01 | ||
Placebo (Placebo ALL Patients) | 憲鹹築衊繭鬱齋淵繭窪 = 餘鹹蓋鏇餘構獵簾遞繭 壓築簾繭夢壓膚積憲遞 (簾鏇憲鹽簾鹹醖鹹憲窪, 膚鏇襯膚夢糧製製衊構 ~ 遞積獵顧壓淵鏇遞壓積) 更多 | ||||||
临床2期 | 42 | 製窪遞顧憲淵憲糧選觸(襯壓繭憲醖網醖艱觸夢) = 遞廠壓顧廠願製製夢鹽 選淵鑰選廠範夢艱簾願 (壓餘鹽夢遞鏇衊壓艱獵 ) | - | 2019-01-03 |
登录后查看更多信息
转化医学
使用我们的转化医学数据加速您的研究。
登录
或
药物交易
使用我们的药物交易数据加速您的研究。
登录
或
核心专利
使用我们的核心专利数据促进您的研究。
登录
或
临床分析
紧跟全球注册中心的最新临床试验。
登录
或
批准
利用最新的监管批准信息加速您的研究。
登录
或
特殊审评
只需点击几下即可了解关键药物信息。
登录
或
提出任何生物医药研究问题
让每一步生物医药决策都精准制胜
基于十亿级生物数据与全球情报的精准 AI，赋能早期药物发现
立即开始免费试用!
智慧芽新药情报库是智慧芽专为生命科学人士构建的基于AI的创新药情报平台，助您全方位提升您的研发与决策效率。
立即接入生物医药数据包
智慧芽新药库数据也通过智慧芽开放平台，以MCP或API服务形式对外开放。立即使用我们的MCP服务定制您的LLM智能体。
生物序列数据库
生物药研发创新
免费使用
化学结构数据库
小分子化药研发创新
免费使用