盐酸美氟尼酮(Mefunidone Hydrochloride) - 药物靶点：TGF-β1_在研适应症：2型糖尿病肾脏病_专利_临床

概要

基本信息

药物类型

小分子化药

别名-

靶点

TGF-β1

作用机制

TGF-β1抑制剂(转化生长因子β1抑制剂)

治疗领域

内分泌与代谢疾病泌尿生殖系统疾病

在研适应症

2型糖尿病肾脏病

非在研适应症-

原研机构

中南大学

在研机构

广州南鑫药业有限公司

中南大学

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-

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关联

3

项与盐酸美氟尼酮相关的临床试验

CTR20230987 / Recruiting临床2期

一项评价盐酸美氟尼酮片治疗2型糖尿病肾病的有效性和安全性的多中心、随机、双盲、安慰剂平行对照研究

主要研究目的：初步评价盐酸美氟尼酮片在2型糖尿病肾病患者中的有效性和安全性。次要研究目的：评价盐酸美氟尼酮片在2型糖尿病肾病患者中的药代动力学特征。

开始日期2023-06-29

申办/合作机构

广州南鑫药业有限公司

[+1]

CTR20211769 / Completed临床1期

盐酸美氟尼酮片在中国健康受试者中多次给药的安全性、耐受性、药代动力学单中心、随机、双盲、安慰剂平行对照的Ⅰb期临床研究

主要目的：评估中国健康受试者多次口服不同剂量盐酸美氟尼酮片的安全性和耐受性。次要目的：评估中国健康受试者多次口服不同剂量盐酸美氟尼酮片的药代动力学（PK）特征。

开始日期2021-10-28

申办/合作机构

广州南鑫药业有限公司

[+1]

CTR20200492 / Completed临床1期

盐酸美氟尼酮片在中国健康受试者中的单次给药、剂量递增的安全性、耐受性、药代动力学及食物影响的单中心、随机、双盲、安慰剂平行对照的Ⅰ期临床研究

主要目的：评估中国健康受试者单次口服不同剂量盐酸美氟尼酮片的安全性和耐受性。

开始日期2020-09-01

申办/合作机构

广州南鑫药业有限公司

[+1]

100 项与盐酸美氟尼酮相关的临床结果

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100 项与盐酸美氟尼酮相关的转化医学

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100 项与盐酸美氟尼酮相关的专利（医药）

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13

项与盐酸美氟尼酮相关的文献（医药）

2024-09-01·Biomedicine & Pharmacotherapy

Mefunidone alleviates silica-induced inflammation and fibrosis by inhibiting the TLR4-NF-κB/MAPK pathway and attenuating pyroptosis in murine macrophages

Article

作者: Peng, Zhangzhe ; Meng, Jie ; Jiang, Mao ; Jiang, Guoliang ; Yao, Tingting ; Tao, Lijian ; Zhang, Xiangyu ; Cheng, Xiaoyun ; Dai, Xiaoqing ; Hu, Gaoyun ; Long, Lingzhi ; He, Yijun

AIMSSilicosis is the most common and severe type of pneumoconiosis, imposing a substantial disease burden and economic loss on patients and society. The pathogenesis and key targets of silicosis are not yet clear, and there are currently no effective treatments available. Therefore, we conducted research on mefunidone (MFD), a novel antifibrotic drug, to explore its efficacy and mechanism of action in murine silicosis.METHODSAcute 7-day and chronic 28-day silicosis models were constructed in C57BL/6J mice by the intratracheal instillation of silica and subsequently treated with MFD to assess its therapeutic potential. The effects of MFD on silica-induced inflammation, pyroptosis, and fibrosis were further investigated using immortalized mouse bone marrow-derived macrophages (iBMDMs).RESULTSIn the 7-day silica-exposed mouse models, MFD treatment significantly alleviated pulmonary inflammation and notably reduced macrophage infiltration into the lung tissue. RNA-sequencing analysis of silica-induced iBMDMs followed by gene set enrichment analysis revealed that MFD profoundly influenced cytokine-cytokine receptor interactions, chemokine signaling, and the toll-like receptor signaling pathways. MFD treatment also markedly reduced the secretion of inflammatory cytokines and chemokines from silica-exposed iBMDMs. Moreover, MFD effectively downregulated the activation of the TLR4-NF-κB/MAPK signaling pathway induced by silica and mitigated the upregulation of pyroptosis markers. Additionally, MFD treatment significantly suppressed the activation of fibroblasts and alveolar epithelial cells co-cultured with silica-exposed mouse macrophages. Ultimately, in the 28-day silica-exposed mouse models, MFD administration led to a substantial reduction in the severity of pulmonary fibrosis.CONCLUSIONMFD mitigates silica-induced pulmonary inflammation and fibrosis in mice by suppressing the TLR4-NF-κB/MAPK signaling pathway and reducing pyroptotic responses in macrophages. MFD could potentially emerge as a novel therapeutic agent for the treatment of silicosis.

2024-07-01·Biochemical Pharmacology

Mefunidone ameliorates acute liver failure in mice by inhibiting MKK4-JNK pathway

Article

作者: Yang, Huixiang ; He, Xin ; Tang, Jie ; Zhang, Yanqiu ; Gu, Lei ; Ma, Ruixue ; Peng, Zhangzhe ; Li, Shenglan

Acute liver failure (ALF) is a critical condition that can lead to substantial liver dysfunction. It is characterized by complex clinical manifestations and rapid progression, presenting significant challenges in diagnosis and treatment. We investigated the protective effect of mefunidone (MFD), a novel antifibrosis pyridone agent, on ALF in mice, and explored its potential mechanism of action. MFD pretreatment can alleviate lipopolysaccharide (LPS) and d-galactosamine (D-GalN)-induced ALF, reduce hepatocyte apoptosis, and reduce inflammation and oxidative stress. Additionally, MFD alleviated LPS/D-GalN-stimulated reactive oxygen species (ROS) production and cell death in AML12 cells. RNA sequencing enrichment analysis showed that MFD significantly affected the Mitogen-Activated Protein Kinase (MAPK) pathway. In vivo and in vitro experiments showed that MFD inhibited MKK4 and JNK phosphorylation. JNK activation caused by MKK4 and JNK activators could eliminate the therapeutic effect of MFD on AML12. In addition, MFD pretreatment alleviated ConA-induced ALF, reduced inflammation and oxidative stress in mice, and reduced mouse mortality. These results suggest that MFD can potentially protect against ALF, partially by inhibiting the MKK4-JNK pathway, and is a promising new therapeutic drug for ALF.

2022-12-01·International Immunopharmacology

Mefunidone ameliorates lipopolysaccharide-induced acute lung injury through inhibiting MAPK signaling pathway and enhancing Nrf2 pathway

Article

作者: Yao, Ting-Ting ; Lv, Xin ; He, Yi-Jun ; Cheng, Xiao-Yun ; Tao, Li-Jian ; Zhang, Yan ; Li, Meng-Yu ; Meng, Jie ; Jiang, Guo-Liang ; He, Rong-Ling ; Li, Qian-Bin ; Hu, Gao-Yun ; Long, Ling-Zhi ; Han, Yuan-Yuan

BACKGROUND AND OBJECTIVEAcute lung injury (ALI) is a life-threatening disease which has high mortality and lacks effective pharmacological treatments. Excessive inflammation and oxidative stress are the key pathogenesis of ALI. Mefunidone (MFD), a novel small molecule compound, displayed anti-inflammation and anti-oxidative stress effects on streptozocin (STZ) and db/db mice in our previous studies. In this study, we aimed to investigate the effects of MFD on lipopolysaccharide (LPS)-induced ALI and explore the potential molecular mechanisms.METHODSWe investigated the effects of MFD on LPS-induced ALI mouse model and LPS-stimulated immortalized mouse bone marrow-derived macrophages (iBMDMs).RESULTSMFD could alleviate pulmonary structure disorder and attenuate pulmonary neutrophils infiltration induced by LPS. MFD could also decreased proinflammatory cytokines release and reduce reactive oxygen species (ROS) generation stimulated by LPS. Further, MFD could significantly reduce LPS-induced phosphorylation levels of mitogen-activated protein kinase (MAPK), increase expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and restore the expressions of antioxidant enzymes.CONCLUSIONOur results firstly supported that MFD effectively protected LPS-induced ALI against inflammation and oxidative stress through inhibiting MAPK signaling pathway and activating Nrf2 pathway.

100 项与盐酸美氟尼酮相关的药物交易

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