常山酮(Halofuginone Hydrobromide) - 药物靶点：Collagen_专利_临床

概要

基本信息

药物类型

小分子化药

别名

(+/-)-trans-7-bromo-6-chloro-3-(3-(3-hydroxy-2-piperidyl)-acetonyl)-4(3H)-quinazolinone、Halofuginone、Halofuginone hydrobromide (USAN)

+ [6]

靶点

Collagen

作用机制

胶原蛋白抑制剂、血管生成抑制剂

治疗领域

肿瘤免疫系统疾病神经系统疾病+ [6]

在研适应症-

非在研适应症

膀胱癌冠状动脉再狭窄肝硬化+ [4]

原研机构

Akashi Therapeutics Inc

在研机构-

非在研机构

Collgard Biopharmaceuticals Ltd.

Akashi Therapeutics Inc

Processa Pharmaceuticals, Inc.

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)-

特殊审评孤儿药 (美国)

登录后查看时间轴

结构

分子式C16H18Br2ClN3O3

InChIKeySJUWEPZBTXEUMU-AJYMSAGVSA-N

CAS号64924-67-0

关联

5

项与常山酮相关的临床试验

NCT02525302 / Terminated临床2期

HT-100 Long-term Safety and Pharmacodynamics in Patients With DMD Who Have Completed Protocols HALO-DMD-01 and HALO-DMD-02

This study, HALO-DMD-03, is a follow-on study to HALO-DMD-01 and HALO-DMD-02, and allows continued open-label access to HT-100 for subjects who have completed these studies. HALO-DMD-03 will provide safety and strength and function data on continuous long-term dosing. Data from this study will be used to inform the safety, tolerability, and dose selection for a future trial of HT-100 in boys with Duchenne Muscular Dystrophy (DMD).

开始日期2015-05-01

申办/合作机构

Akashi Therapeutics Inc

NCT01978366 / Terminated临床2期

An Open Label Extension Study of HT-100 in Patients With Duchenne Muscular Dystrophy Who Have Completed Protocol HALO-DMD-01

This study is designed to provide 6-months continuous dosing with the study medication, called HT-100, on participants who successfully completed the predecessor study (HALO-DMD-01). The main purpose of this study is to assess chronic safety, tolerability, pharmacodynamic activity (testing the drug's effect on DMD) and population pharmacokinetics (measuring how much drug is in the bloodstream) in participants with a broad spectrum of Duchenne muscular dystrophy (DMD).

开始日期2013-10-01

申办/合作机构

Processa Pharmaceuticals, Inc.

NCT01847573 / Terminated临床1/2期

A Phase 1b Open Label, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT-100 in Patients With Duchenne Muscular Dystrophy

The main purpose of this study is to test the safety and tolerability of different, increasing doses of an experimental medication called HT-100 in boys and young men with Duchenne muscular dystrophy (DMD). The study medication, HT-100, is a medicine that may help promote healthy muscle regeneration, diminish inflammation and the resulting damage to muscle, and decrease the scar tissue that forms in the muscles of children with DMD. In this study, pharmacokinetic sampling, or measurements of the amount of HT-100 in the bloodstream will also be taken.

开始日期2013-05-01

申办/合作机构

Processa Pharmaceuticals, Inc.

100 项与常山酮相关的临床结果

登录后查看更多信息

100 项与常山酮相关的转化医学

登录后查看更多信息

100 项与常山酮相关的专利（医药）

登录后查看更多信息

575

项与常山酮相关的文献（医药）

2024-12-01·Journal of Molecular Histology

Halofuginone ameliorates the susceptibility to atrial fibrillation by activating the PI3K/Akt signaling pathway

Article

作者: Zhao, Xiaolong ; Shen, Chunjian ; Zhang, Jing ; Xu, Feng

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Halofuginone (HF) exerts beneficial effects on organ fibrosis, periodontitis, and cancer. However, the effect of HF against AF remains unknown. During the induction of AF, the rats were intragastrically administered HF (5 mg/kg and 10 mg/kg) daily for 7 consecutive days. Cardiac function was evaluated through echocardiographic analysis. The presence of pathological changes and interstitial fibrosis in the left atrial tissues were investigated. Intracellular Ca²⁺ homeostasis and mitochondrial function in atrial tissues were evaluated. The activation of the PI3K/Akt signaling pathway was examined, and an allosteric Akt inhibitor, MK-2206, was applied to confirm the involvement of the PI3K/Akt signaling pathway in the protection against AF by HF. The administration of HF resulted in a prolongation of the atrial effective refractory period (AERP), a reduction in both the duration and inducibility of AF, and a decrease in atrial weight, heart weight, atrial weight/body weight ratio, and heart weight/body weight ratio in rats with AF. In addition, the administration of HF resulted in a reduction in left atrial diameter (LAD) and an increase in left ventricular internal diameter diastolic (LVIDd), ejection fraction (EF), and fractional shortening (FS), while having no effect on left ventricular internal diameter systolic (LVIDs). The pathological changes and cardiac fibrosis observed in rats with AF were mitigated by HF. Moreover, HF enhanced mitochondrial function, suppressed cardiomyocyte apoptosis, and activated the PI3K/Akt pathway in AF rats. Furthermore, the protective effect against AF was also observed in an in vitro model. The effects of HF on fibrosis markers, intracellular Ca²⁺ homeostasis, mitochondrial function, and cardiac apoptosis were blocked by MK-2206. HF alleviated the susceptibility to AF in vivo and in vitro via the activation of the PI3K/Akt signaling pathway.

2024-10-07·Journal of Cell Biology

Integrated stress response activator halofuginone protects mice from diabetes-like phenotypes

Article

作者: Bertolotti, Anne ; Rai, Shashank ; Szaruga, Maria ; Pitera, Aleksandra P.

The integrated stress response (ISR) is a vital signaling pathway initiated by four kinases, PERK, GCN2, HRI and PKR, that ensure cellular resilience and protect cells from challenges. Here, we investigated whether increasing ISR signaling could rescue diabetes-like phenotypes in a mouse model of diet-induced obesity (DIO). We show that the orally available and clinically approved GCN2 activator halofuginone (HF) can activate the ISR in mouse tissues. We found that daily oral administration of HF increases glucose tolerance whilst reducing weight gain, insulin resistance, and serum insulin in DIO mice. Conversely, the ISR inhibitor GSK2656157, used at low doses to optimize its selectivity, aggravates glucose intolerance in DIO mice. Whilst loss of function mutations in mice and humans have revealed that PERK is the essential ISR kinase that protects from diabetes, our work demonstrates the therapeutic value of increasing ISR signaling by activating the related kinase GCN2 to reduce diabetes phenotypes in a DIO mouse model.

2024-09-02·ChemBioChem

Chemoproteomic Strategy Identifies PfUCHL3 as the Target of Halofuginone

Article

作者: Zhao, Mei‐Mei ; Zhao, Mei-Mei ; Wei, Chun-Yan ; Yu, Si-Miao ; Zheng, Yong‐Zhe ; Zeng, Ke‐Wu ; Wei, Chun‐Yan ; Yu, Si‐Miao ; Liu, Zheng‐Ping ; Zhang, Ji-Chao ; Tu, Peng-Fei ; Tu, Peng‐Fei ; Zheng, Yong-Zhe ; Zeng, Ke-Wu ; Liu, Zheng-Ping ; Zhang, Ji‐Chao ; Wang, Heng

AbstractThe human malaria parasite Plasmodium falciparum (P. falciparum) continues to pose a significant public health challenge, leading to millions of fatalities globally. Halofuginone (HF) has shown a significant anti‐P. falciparum effect, suggesting its potential as a therapeutic agent for malaria treatment. In this study, we synthesized a photoaffinity labeling probe of HF to identify its direct target in P. falciparum. Our results reveal that ubiquitin carboxyl‐terminal hydrolase 3 (PfUCHL3) acts as a crucial target protein of HF, which modulates parasite growth in the intraerythrocytic cycle. In particular, we discovered that HF potentially forms hydrogen bonds with the Leu10, Glu11, and Arg217 sites of PfUCHL3, thereby inducing an allosteric effect by promoting the embedding of the helix 6’ region on the protein surface. Furthermore, HF disrupts the expression of multiple functional proteins mediated by PfUCHL3, specifically those that play crucial roles in amino acid biosynthesis and metabolism in P. falciparum. Taken together, this study highlights PfUCHL3 as a previously undisclosed druggable target of HF, which contributes to the development of novel anti‐malarial agents in the future.

100 项与常山酮相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D04413	常山酮	-	DB04866

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
杜氏肌营养不良症	临床2期	美国	Processa Pharmaceuticals, Inc.	2013-10-01
膀胱癌	临床2期	英国	Collgard Biopharmaceuticals Ltd.	-
膀胱癌	临床2期	以色列	Collgard Biopharmaceuticals Ltd.	-
冠状动脉再狭窄	临床2期	美国	-	-
肝硬化	临床2期	以色列	Collgard Biopharmaceuticals Ltd.	-
肿瘤	临床2期	欧洲	Collgard Biopharmaceuticals Ltd.	-
肿瘤	临床2期	荷兰	-	-
肿瘤	临床2期	比利时	-	-
肾纤维化	临床2期	以色列	Collgard Biopharmaceuticals Ltd.	-
系统性硬皮病	临床2期	英国	Collgard Biopharmaceuticals Ltd.	-

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ARVO2022	N/A	-	-	Halofuginone	構構鬱鑰衊構願艱夢鏇(膚鹹觸糧製蓋鹹壓願鑰) = 遞觸醖鹽淵繭遞窪夢齋鬱壓淵製範願願壓網網 (蓋願繭憲鬱構製憲窪蓋 ) 更多	-	2022-05-01
				PBS	構構鬱鑰衊構願艱夢鏇(膚鹹觸糧製蓋鹹壓願鑰) = 蓋簾餘積醖艱觸窪鏇蓋鬱壓淵製範願願壓網網 (蓋願繭憲鬱構製憲窪蓋 ) 更多
ASTRO	N/A	肺癌	-	Halofuginone (Control group)	衊遞鑰積願鑰鑰繭淵憲(糧夢衊醖遞簾鏇鹽願憲) = Immunohistochemistry study revealed decrease level of TGF-Î²1 expression in the halofuginone group and the combined group than in any other groups. The TGF-Î²1 level measured with ELISA also showed the similar results 齋築夢衊夢簾蓋壓鬱夢 (選鏇選壓襯夢範膚醖蓋 ) 更多	-	2012-11-01
				Halofuginone group