氟非尼酮(Fluorofenidone) - 药物靶点：TGF-β1 x p38γ_在研适应症：肝纤维化，慢性乙型肝炎，肾纤维化_专利_临床

概要

基本信息

药物类型

小分子化药

别名

AKF-PD

靶点

TGF-β1 x p38γ

作用机制

TGF-β1抑制剂(转化生长因子β1抑制剂)、p38γ抑制剂(P38 丝裂原活化蛋白激酶-γ抑制剂)

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

+ [1]

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)临床2期

特殊审评特殊审批 (中国)

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结构

分子式C12H10FNO

InChIKeyJDZYVVUJIQYGRX-UHFFFAOYSA-N

CAS号848353-85-5

关联

5

项与氟非尼酮相关的临床试验

CTR20213016 / RecruitingN/A

氟非尼酮胶囊在肝功能损害受试者的药代动力学和安全性研究（单中心、开放）

主要目的：比较氟非尼酮胶囊在轻度肝损害受试者和肝功能正常受试者的药代动力学特征。次要目的：评价氟非尼酮胶囊在肝功能损害受试者中的安全性。

开始日期2022-03-18

申办/合作机构

海口市医药总公司

[+1]

CTR20211557 / Active, not recruiting临床2期

以富马酸丙酚替诺福韦片作为基础治疗，评估不同剂量的氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的有效性和安全性的多中心、随机、双盲、安慰剂、平行对照 II 期临床试验

主要目的：与安慰剂对照，初步评价不同剂量氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的有效性。次要目的：初步评价不同剂量氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的安全性。

开始日期2021-11-22

申办/合作机构

海口市医药总公司

[+1]

CTR20211372 / CompletedN/A

富马酸丙酚替诺福韦片对氟非尼酮胶囊的药代动力学影响试验

主要目的：评价富马酸丙酚替诺福韦片对中国健康成人受试者餐后状态下口服氟非尼酮胶囊药代动力学的影响。次要研究目的：评价中国健康成人受试者餐后状态下单独口服氟非尼酮胶囊、随餐单独服用富马酸丙酚替诺福韦片或餐后状态下同时服用富马酸丙酚替诺福韦片和氟非尼酮时的安全性。

开始日期2021-07-06

申办/合作机构

海口市医药总公司

[+1]

100 项与氟非尼酮相关的临床结果

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100 项与氟非尼酮相关的转化医学

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100 项与氟非尼酮相关的专利（医药）

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61

项与氟非尼酮相关的文献（医药）

2023-12-01·Cell biochemistry and biophysics

Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function.

Article

作者: Lu, Miaomiao ; Zhou, Hongli ; Liu, Wenlin ; Xing, Di ; Dong, Haonan

BACKGROUNDFluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.METHODSA renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.RESULTSCompared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.CONCLUSIONThe results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.

2023-11-01·Biochemical and Biophysical Research Communications

Fluorofenidone enhances cardiac contractility by stimulating CICR and CaV1.2

Article

作者: Ávila, Guillermo

Fluorofenidone (AKF-PD) is a novel pyridone derivative that inhibits fibrosis and inflammation in many tissues. Accordingly, it has been effective in disease models, such as liver failure, nephropathy, and pulmonary fibrosis. However, its potential role in cardiac physiology and pathology has yet to be elucidated. Thus, this paper investigated a possible functional impact of AKF-PD on adult rat cardiac myocytes. Cells were kept in culture for 1-2 days under either control conditions or the presence of AKF-PD (500 μM). They were next examined concerning cell contractility, intracellular Ca²⁺ homeostasis, and activity of voltage-gated Ca²⁺ channels. Remarkably, AKF-PD enhanced the percentage of cell shortening and rates of both contraction and relaxation by nearly 100%. A stimulus in Ca²⁺-induced Ca²⁺ release (CICR) most likely accounts for these effects because AKF-PD also increased the magnitude of electrically evoked Ca²⁺ transients. Of note, the compound did not alter the peak value of caffeine-elicited Ca²⁺ transients, indicating stimulation of CICR at constant sarcoplasmic reticulum Ca²⁺ load. Since CICR is triggered by the entry of Ca²⁺ through Ca_V1.2 (I_Ca), a possible effect on these Ca²⁺ channels was also investigated. AKF-PD increased the magnitude of both I_Ca and maximal macroscopic Ca²⁺ conductance (G_max) by about 50%. However, no differences were found in either voltage dependence of inactivation or the amount of maximal immobilization-resistant charge movement (Q_max). Thus, the effect on I_Ca could be explained by a higher channel's open probability (P_o) rather than a greater abundance of channel proteins. Additional data indicate that AKF-PD reduces the rate of Ca²⁺ extrusion in the presence of caffeine, suggesting inhibition of the Na/Ca exchanger. Overall, these results indicate that AKF-PD upregulates the P_o of Ca_V1.2 and then sequentially enhances I_Ca, CICR, and contractility. Therefore, the novel compound is also a candidate to be tested in cardiac disease models.

2023-09-04·Molecular pharmaceutics

Complexation of Fluorofenidone by Cucurbit[7]uril and β-Cyclodextrin: Keto-Enol Tautomerization to Enhance the Solubility.

Article

作者: Lu, Tong-Bu ; Chen, Hua-Yu ; Huang, Yong-Liang ; Chen, Jia-Mei ; Ma, Wen-Juan

This study is designed to compare drug encapsulation by cucurbit[7]uril and β-cyclodextrin, using fluorofenidone as a model drug. Single-crystal X-ray diffraction analysis was employed to successfully determine the crystal structures of fluorofenidone·H⁺@cucurbit[7]uril Form, fluorofenidone@cucurbit[7]uril Form, and fluorofenidone@β-cyclodextrin Form. Keto-enol tautomerization of fluorofenidone mediated by cucurbit[7]uril in acid solution is confirmed by crystal structures, pH titration, and nuclear magnetic resonance experiments. However, β-cyclodextrin cannot cause the keto-enol tautomerization of fluorofenidone under similar conditions. The phase solubility study demonstrates that cucurbit[7]uril has a much higher solubilization capacity for fluorofenidone than β-cyclodextrin in 0.1 M HCl since the K_c values of fluorofenidone with cucurbit[7]uril and β-cyclodextrin were 1223.97 ± 452.68 and 78.49 ± 10.56 M^-1, respectively. Excellent solubility can be attributed to the keto-enol tautomerization of fluorofenidone under the conditions of cucurbit[7]uril in acid solution. The enol form of fluorofenidone is encapsulated by cucurbit[7]uril by hydrogen bonding interaction and hydrophobic interaction to increase binding affinity. Rat pharmacokinetic studies demonstrate that the area under the plasma concentration-time curve from time 0 to 7 h value of fluorofenidone@cucurbit[7]uril complex is 1.70-fold greater than that of free fluorofenidone, and the mean residence time from time 0 to 7 h is slightly prolonged from 1.29 to 1.76 h (P < 0.01) after oral administration. However, no significant difference is found between fluorofenidone and fluorofenidone@β-cyclodextrin complex. This work indicates that the induction of keto-enol tautomerization of drugs using macrocyclic molecules has the potential to be an effective method to improve their solubility and bioavailability, providing valuable insights for the application of macrocyclic molecules in the biomedical field.

100 项与氟非尼酮相关的药物交易

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研发状态

10 条进展最快的记录,

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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	中国	中南大学	2021-11-22
肝纤维化	临床2期	中国	海口市医药总公司	2021-11-22
慢性乙型肝炎	临床2期	中国	海口市医药总公司	2021-11-22
慢性乙型肝炎	临床2期	中国	中南大学	2021-11-22
肾纤维化	临床1期	中国	海南海药股份有限公司	-
肾纤维化	临床1期	中国	中南大学	-
肾纤维化	临床1期	中国	Dierepharma HK Ltd	-
肝硬化	临床前	中国	海口市医药总公司	2018-11-19
肝硬化	药物发现	中国	中南大学	2018-11-19