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更新于：2025-08-30
Cilofexor tromethamine
更新于：2025-08-30
概要
基本信息
在研机构- |
最高研发阶段终止临床3期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构/序列
分子式C32H33Cl3N4O8 |
InChIKeyCUWTTWVBVUZPAP-UHFFFAOYSA-N |
CAS号2253764-93-9 |
关联
13
项与 Cilofexor tromethamine 相关的临床试验NCT04060147
A Proof-of-Concept, Open-Label Study Evaluating the Safety and Tolerability of Cilofexor in Subjects With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
NCT03987074
A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)
ACTRN12619000655145
A Phase 1 Open-Label, Parallel-Group, Two-Treatment, Single-Dose Study to Evaluate the Pharmacokinetics of GS-9674 and GS-0976 in Subjects with Normal Renal Function and Severe Renal Impairment
100 项与 Cilofexor tromethamine 相关的临床结果
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100 项与 Cilofexor tromethamine 相关的转化医学
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100 项与 Cilofexor tromethamine 相关的专利（医药）
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72
项与 Cilofexor tromethamine 相关的文献（医药）2025-01-01EUROPEAN JOURNAL OF PHARMACOLOGY
Cilostazol counteracts mitochondrial dysfunction in hepatic encephalopathy rat model: Insights into the role of cAMP/AMPK/SIRT1/ PINK-1/parkin hub and p-CREB /BDNF/ TrkB neuroprotective trajectory
Article
作者: Hassan, Noha F ; Gad, Enas S ; El-Ansary, Amira R ; El-Ansary, Mona R ; Aldossary, Sara A ; Abd El-Galil, Mona M ; Abd-El-Hamid, Asmaa Hassan
A devasting stage of chronic hepatic dysfunction is strictly correlated with neurological impairment, signifying hepatic encephalopathy (HE). HE is a multifactorial condition; therefore, hyperammonemia, oxidative stress, neuroinflammation, and mitochondrial dysfunction interplay in HE's progressive development. Cilostazol (Cilo) has shown promising neuroprotective and hepatoprotective effectiveness in different neuronal and hepatic disorders; however, its efficiency against HE hasn't yet been explored. This study aimed to investigate the protective role of Cilo against thioacetamide (TAA)-induced HE in rats targeting mitochondrial dysfunction via modulation of Adenosine monophosphate-activated protein kinase (AMPK)/Silent information regulator 1 (SIRT1) dependent pathways. Rats were allocated into three groups: the normal control group, the TAA group received (100 mg/kg, three times per week, for six weeks) to induce HE, and the Cilo group received (Cilo 100 mg/kg/day for six weeks, oral gavage) concurrently with TAA. Cilo counteracted HE indicated in the enhancement of cognitive impairment and the motor performance of rats (P < 0.0001), modulation AMPK/SIRT1signaling pathway causing reduction of NF-kB p65 (P < 0.0001) evoked inflammation along with histopathological alterations and glial fibrillary acidic protein (GFAP) immunoreactivity (P < 0.0001), restoration nuclear factor E2-related factor 2 (Nrf2) (P < 0.0001) antioxidant effects, reduction of Bax and elevation of Bcl2 immunoreactivity (P < 0.0001) in addition to boosting mitochondrial biogenesis by upregulation of PTEN-induced kinase-1 (PINK-1)/Parkin (P < 0.0001)and restoration of Brain-derived neurotrophic factor (BDNF) (P = 0.0002)/tropomyosin-related kinase B (TrkB) (P < 0.0001)/cAMP response element-binding (CREB) (P < 0.0001) neuroprotective axis. Collectively, Cilo activates the SIRT1 trajectory to abridge mitochondrial dysfunction invigorated in the HE rat model via restoration of mitochondrial hemostasis.
2025-01-01EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Design, synthesis, and biological evaluation of novel highly potent FXR agonists bearing piperidine scaffold
Article
作者: Geng, Xinqian ; Wang, Wenxin ; Liu, Yuxia ; Liao, Zibin ; Chen, Yisi ; Li, Zheng ; Yang, Yuanqian ; Yang, Ying ; Huang, Zibin ; Cai, Zongyu ; Liang, Zhilin
Metabolic dysfunction-associated steatohepatitis (MASH) has become a serious threat to human health, which exhibited an increasing prevalence globally. Recently, the farnesoid X receptor (FXR) has been identified as a promising strategy for the treatment of MASH by regulating multiple pathogenesis. In this study, a new series of FXR agonists bearing piperidine scaffold was designed to reduce the high lipophilicity of the existing FXR agonists. After comprehensive multiparameter optimization, LZ-007 was discovered as a highly potent FXR agonist with suitable stability in liver microsomes of multiple species. LZ-007 exhibited highly oral bioavailability and targeted tissue exposure in the liver and ileum, while the plasma exposure is low, which might minimize the systemic side effects. Moreover, LZ-007 was significantly up-regulated the expressions of FXR and its downstream genes in the liver and ileum. In MASH model, LZ-007 exerted potent anti-MASH effects by regulating the multiple signal pathways related to lipid metabolism, oxidative stress, inflammation and fibrosis. In a 30-day toxicity study, no apparent adverse effects were observed in LZ-007 treated groups, even at the high doses of 250 and 500 mg/kg. With the positive pharmacodynamics and safety profiles, LZ-007 is worthy of further evaluation as a new anti-MASH agent.
2024-12-01AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response in Cyp2c70 knockout mice with a humanized bile acid composition
Article
作者: Luedde, Tom ; Bennett, Ashley L. ; Mayatepek, Ertan ; Dawson, Paul A. ; Ebert, Matthias ; Klindt, Caroline ; Truong, Jennifer K. ; Herebian, Diran ; Pachura, Kimberly J. ; Karpen, Saul J.
Bile acids are implicated as a common contributor to the pathogenesis and progression of cholestatic liver disease. Using a mouse model with a humanized bile acid composition, we demonstrated that mono and combination therapy using an IBAT inhibitor and FXR nonsteroidal agonist were effective at reducing hepatic bile acid accretion and reversing liver injury, without reducing hepatic bile acid hydrophobicity. The findings support the concept of a therapeutically tractable threshold for bile acid-induced liver injury.
51
项与 Cilofexor tromethamine 相关的新闻（医药）2025-08-18
财报并购疫苗临床3期抗体药物偶联物
2025-08-12
·药时空
财报ASH会议临床2期临床3期突破性疗法
2025-08-11
·医药速览
财报临床3期临床2期ASH会议
100 项与 Cilofexor tromethamine 相关的药物交易
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外链
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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 |
|---|---|---|---|---|
| 原发性硬化性胆管炎 | 临床3期 | 美国 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 日本 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 澳大利亚 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 奥地利 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 比利时 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 加拿大 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 丹麦 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 芬兰 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 法国 | 2019-03-27 | |
| 原发性硬化性胆管炎 | 临床3期 | 德国 | 2019-03-27 |
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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1期 | 11 | 鹹觸積憲鏇憲選餘範遞(構鹽顧淵鹹艱壓簾憲鏇) = fatigue (2/11 [18.2%]) 鹹築獵製遞蓋鬱淵製衊 (壓襯淵觸窪獵遞壓鏇構 ) 更多 | 积极 | 2024-07-01 | |||
临床3期 | 419 | (Cilofexor 100 mg (Blinded Phase)) | 範簾蓋網壓繭蓋憲膚鏇 = 淵醖鬱繭積網醖鑰製積 廠鬱構繭憲糧構衊蓋膚 (顧蓋艱範觸築遞鏇壓鑰, 網遞顧齋齋壓選築醖齋 ~ 積襯膚壓顧餘夢願顧築) 更多 | - | 2023-11-29 | ||
Placebo (Placebo (Blinded Phase)) | 範簾蓋網壓繭蓋憲膚鏇 = 製遞繭蓋齋夢願鬱鑰齋 廠鬱構繭憲糧構衊蓋膚 (顧蓋艱範觸築遞鏇壓鑰, 構網選鹹壓築壓齋艱鏇 ~ 窪窪積糧壓築網糧獵觸) 更多 | ||||||
临床1期 | 11 | 夢鬱鑰齋鹹膚獵願壓選 = 顧襯鬱鹽願遞鹽範觸艱 鏇衊觸襯鹽窪鬱範鏇廠 (襯鬱獵繭繭鹽廠襯遞獵, 糧醖齋簾顧醖獵築簾餘 ~ 顧顧淵糧齋網糧憲願顧) 更多 | - | 2023-07-27 | |||
临床3期 | 11 | 膚範鏇糧糧齋顧膚築築(構構選簾窪醖願築願鑰) = 簾窪廠糧襯簾糧鏇網憲 齋簾窪膚願鹽網艱製網 (膚壓窪構顧積淵獵窪窪 ) 更多 | 积极 | 2022-06-23 | |||
临床2期 | 108 | 齋觸廠糧衊範壓鏇願淵(鑰鑰築繭蓋衊築製簾糧) = Treatments were well tolerated - the incidence of adverse events was similar across groups (73-90%) and most events were gastrointestinal in nature. 築製糧遞觸窪遞蓋範衊 (鏇構齋鬱範鑰膚餘艱蓋 ) 更多 | 积极 | 2022-04-16 | |||
临床2期 | 66 | 淵選鹹遞觸糧願構鏇醖(鑰窪積窪顧選範糧壓製) = most treatment-emergent adverse events were Grade 1 to 2 severity 醖壓觸齋醖願壓窪艱襯 (製構遞鬱鏇鏇構鹽壓餘 ) 更多 | 积极 | 2022-01-06 | |||
临床2期 | 109 | (Semaglutide) | 壓淵醖願製網衊餘齋鏇 = 築壓夢網範觸鬱築醖積 廠鹽糧鏇餘廠窪壓廠構 (製糧鹽願鑰壓醖壓艱鹽, 蓋壓獵獵憲繭廠艱網網 ~ 齋憲遞選鏇觸壓醖範鑰) 更多 | - | 2021-07-15 | ||
(Semaglutide + Firsocostat 20 mg) | 壓淵醖願製網衊餘齋鏇 = 選鏇膚鑰鹽製膚觸鏇顧 廠鹽糧鏇餘廠窪壓廠構 (製糧鹽願鑰壓醖壓艱鹽, 鬱顧糧鬱網顧觸襯壓顧 ~ 壓廠顧蓋壓壓壓鹹獵製) 更多 | ||||||
临床2期 | 12 | 願築鹽齋網衊糧簾顧鏇(鏇積鑰蓋繭壓網壓構廠) = There were no serious adverse events but short intervals of cardiac arrhythmia recorded in 2 patients led to termination of the study. 蓋構醖鑰構窪糧窪鑰鹹 (蓋窪鏇觸築願鏇夢齋鏇 ) | 积极 | 2021-05-01 | |||
临床2期 | 395 | Placebo to match SEL | 觸鏇廠淵壓繭築鹽餘願 = 醖蓋齋膚鏇簾遞積淵簾 願鹽範網願鑰遞簾壓願 (顧壓遞蓋襯醖壓範獵衊, 鏇齋願鹽築鬱窪遞遞憲 ~ 鬱鹹網鹹鹹襯鹽網獵夢) 更多 | - | 2020-12-03 | ||
临床1期 | 57 | (Cohort 1: Mild Hepatic Impairment) | 選鏇艱壓觸積鬱選壓網(醖網製築構顧繭網艱衊) = 襯選顧廠構鬱壓繭蓋觸 遞壓觸鹽鬱積鹽積衊鹽 (糧鬱襯遞積淵膚範鹽鹽, 2175.34) 更多 | - | 2020-09-30 | ||
(Cohort 1: Normal Hepatic Function) | 選鏇艱壓觸積鬱選壓網(醖網製築構顧繭網艱衊) = 糧簾願鬱網餘願衊襯築 遞壓觸鹽鬱積鹽積衊鹽 (糧鬱襯遞積淵膚範鹽鹽, 1230.49) 更多 |
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