硝酸布康唑(Butoconazole Nitrate) - 药物靶点：fungal CYP51A1_在研适应症：念珠菌病，外阴阴道念珠菌病_专利_临床

概要

基本信息

药物类型

小分子化药

别名

1-[4-(4-Chloro-phenyl)-2-(2,6-dichloro-phenylsulfanyl)-butyl]-1H-imidazole、Butoconazole nitrate (USP)

+ [5]

靶点

fungal CYP51A1

作用机制

fungal CYP51A1抑制剂(真菌细胞色素P450家族成员51抑制剂)

治疗领域

感染泌尿生殖系统疾病

在研适应症

念珠菌病外阴阴道念珠菌病

非在研适应症-

原研机构

Bayer AG

在研机构

济南海泰医药科技有限公司AMAG Pharma USA, Inc.济南宏瑞创博医药科技开发有限公司

非在研机构

扬子江药业集团有限公司

Bayer AG

最高研发阶段批准上市

首次获批日期

美国 (1995-12-21),

念珠菌病

最高研发阶段(中国)批准上市

特殊审评-

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结构

分子式C19H18Cl3N3O3S

InChIKeyZHPWRQIPPNZNML-UHFFFAOYSA-N

CAS号64872-77-1

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关联

13

项与硝酸布康唑相关的临床试验

CTR20132863 / Active, not recruiting临床2期

硝酸布康唑阴道凝胶治疗外阴阴道假丝酵母菌病有效性安全性，随机单盲阳性药平行对照、多中心临床试验

进一步评价硝酸布康唑阴道凝胶治疗外阴阴道假丝酵母菌病（VVC）的有效性和安全性。

开始日期2015-07-12

申办/合作机构

济南宏瑞创博医药科技开发有限公司

CTR20140731 / Recruiting临床2期

评价不同剂量硝酸布托康唑栓治疗外阴阴道假丝酵母菌病的疗效及安全性Ⅱa期临床研究方案

评价不同剂量硝酸布托康唑栓治疗外阴阴道假丝酵母菌病的临床疗效及安全性，为进一步临床验证试验提供科学剂量参考。

开始日期2014-09-19

申办/合作机构

济南海泰医药科技有限公司

CTR20131750 / Completed临床2期

硝酸布康唑阴道凝胶治疗外阴阴道假丝酵母菌病有效性和安全性，随机单盲、阳性药平行对照、多中心临床试验

评价硝酸布康唑阴道凝胶治疗外阴阴道假丝酵母菌病的有效性、安全性，为Ⅱb期临床试验提供最佳给药方案依据

开始日期2013-10-31

申办/合作机构

济南宏瑞创博医药科技开发有限公司

100 项与硝酸布康唑相关的临床结果

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100 项与硝酸布康唑相关的转化医学

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100 项与硝酸布康唑相关的专利（医药）

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68

项与硝酸布康唑相关的文献（医药）

2024-04-01·Archives of Biochemistry and Biophysics

Identifying novel aryl hydrocarbon receptor (AhR) modulators from clinically approved drugs: In silico screening and In vitro validation

Article

作者: Mosa, Farag E S ; El-Kadi, Ayman O S ; El-Ghiaty, Mahmoud A ; Alqahtani, Mohammed A ; Barakat, Khaled

The aryl hydrocarbon receptor (AhR) functions as a vital ligand-activated transcription factor, governing both physiological and pathophysiological processes. Notably, it responds to xenobiotics, leading to a diverse array of outcomes. In the context of drug repurposing, we present here a combined approach of utilizing structure-based virtual screening and molecular dynamics simulations. This approach aims to identify potential AhR modulators from Drugbank repository of clinically approved drugs. By focusing on the AhR PAS-B binding pocket, our screening protocol included binding affinities calculations, complex stability, and interactions within the binding site as a filtering method. Comprehensive evaluations of all DrugBank small molecule database revealed ten promising hits. This included flibanserin, butoconazole, luliconazole, naftifine, triclabendazole, rosiglitazone, empagliflozin, benperidol, nebivolol, and zucapsaicin. Each exhibiting diverse binding behaviors and remarkably very low binding free energy. Experimental studies further illuminated their modulation of AhR signaling, and showing that they are consistently reducing AhR activity, except for luliconazole, which intriguingly enhances the AhR activity. This work demonstrates the possibility of using computational modelling as a quick screening tool to predict new AhR modulators from extensive drug libraries. Importantly, these findings hold immense therapeutic potential for addressing AhR-associated disorders. Consequently, it offers compelling prospects for innovative interventions through drug repurposing.

2024-03-01·Liver International

The integrated stress response‐related expression of CHOP due to mitochondrial toxicity is a warning sign for DILI liability

Article

作者: van de Water, Bob ; Eakins, Julie ; de Jong, Brechtje ; Pellegrino‐Coppola, Damiano ; Vlasveld, Matthijs ; Walker, Paul ; Callegaro, Giulia ; Lok, Samantha ; van Oost, Siddh ; Wink, Steven ; Fisher, Ciarán ; Burger, Gerhard

AbstractBackground and AimsDrug‐induced liver injury (DILI) is one of the most frequent reasons for failure of drugs in clinical trials or market withdrawal. Early assessment of DILI risk remains a major challenge during drug development. Here, we present a mechanism‐based weight‐of‐evidence approach able to identify certain candidate compounds with DILI liabilities due to mitochondrial toxicity.MethodsA total of 1587 FDA‐approved drugs and 378 kinase inhibitors were screened for cellular stress response activation associated with DILI using an imaging‐based HepG2 BAC‐GFP reporter platform including the integrated stress response (CHOP), DNA damage response (P21) and oxidative stress response (SRXN1).ResultsIn total 389, 219 and 104 drugs were able to induce CHOP‐GFP, P21‐GFP and SRXN1‐GFP expression at 50 μM respectively. Concentration response analysis identified 154 FDA‐approved drugs as critical CHOP‐GFP inducers. Based on predicted and observed (pre‐)clinical DILI liabilities of these drugs, nine antimycotic drugs (e.g. butoconazole, miconazole, tioconazole) and 13 central nervous system (CNS) agents (e.g. duloxetine, fluoxetine) were selected for transcriptomic evaluation using whole‐genome RNA‐sequencing of primary human hepatocytes. Gene network analysis uncovered mitochondrial processes, NRF2 signalling and xenobiotic metabolism as most affected by the antimycotic drugs and CNS agents. Both the selected antimycotics and CNS agents caused impairment of mitochondrial oxygen consumption in both HepG2 and primary human hepatocytes.ConclusionsTogether, the results suggest that early pre‐clinical screening for CHOP expression could indicate liability of mitochondrial toxicity in the context of DILI, and, therefore, could serve as an important warning signal to consider during decision‐making in drug development.

2024-01-11·Journal of Medicinal Chemistry1区 · 医学

Design and Discovery of Novel NLRP3 Inhibitors and PET Imaging Radiotracers Based on a 1,2,3-Triazole-Bearing Scaffold

1区 · 医学

Article

作者: Liu, Yan ; Tanzi, Rudolph ; Xu, Yulong ; Kaur, Baljit ; Wang, Changning ; Biby, Savannah ; Zhang, Shijun ; Xu, Yiming ; Zhang, Can ; Bagdasarian, Frederick Andrew ; Wey, Hsiao-Ying

The NOD-like receptor (NLR) family pyrin-domain-containing 3 (NLRP3) inflammasome, an essential component of the innate immune system, has been emerging as a viable drug target and a potential biomarker for human diseases. In our efforts to develop novel small molecule NLRP3 inhibitors, a 1-(5-chloro-2-methoxybenzyl)-4-phenyl-1H-1,2,3-triazole scaffold was designed via a rational approach based on our previous leads. Structure-activity relationship studies and biophysical studies identified a new lead compound 8 as a potent (IC₅₀: 0.55 ± 0.16 μM), selective, and direct NLRP3 inhibitor. Positron emission tomography (PET) imaging studies of [¹¹C]8 demonstrated its rapid and high brain uptake as well as fast washout in mice and rhesus macaque. Notably, plasma kinetic analysis of this radiotracer from the PET/magnetic resonance imaging studies in rhesus macaque suggested radiometabolic stability. Collectively, our data not only encourage further studies of this lead compound but also warrant further optimization to generate additional novel NLRP3 inhibitors and suitable central nervous system PET radioligands with translational promise.

100 项与硝酸布康唑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00880	硝酸布康唑	G01AF15	DB00639

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
念珠菌病	中国	AMAG Pharma USA, Inc.	2009-01-24

未上市

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
外阴阴道念珠菌病	临床前	中国	扬子江药业集团有限公司	2013-05-19

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01039584 (CTgov)	N/A	外阴阴道念珠菌病	611	Butoconazole Nitrate Vaginal Cream (Test Product)	遞獵遞廠鹹齋醖蓋鏇鑰(鹹範鹽顧醖鏇醖繭餘夢) = 鹹選艱餘簾製獵廠衊夢窪壓壓齋餘廠構鹹壓鑰 (鬱夢鹹憲鏇觸顧選廠鏇, 衊糧鬱襯簾簾蓋鏇醖製 ~ 衊積鑰餘窪願鬱製襯鹽) 更多	-	2013-01-21
				Gynazole 1 vaginal cream (Reference Product)	遞獵遞廠鹹齋醖蓋鏇鑰(鹹範鹽顧醖鏇醖繭餘夢) = 獵夢繭夢獵鹽鹽觸簾窪窪壓壓齋餘廠構鹹壓鑰 (鬱夢鹹憲鏇觸顧選廠鏇, 顧繭鏇壓鹹鬱齋窪網夢 ~ 蓋鑰積積觸積醖顧顧淵) 更多