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

作用方式

抑制剂

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

权益机构-

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/序列

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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167

项与硝酸布康唑相关的文献（医药）

2025-03-24·Journal of Biomolecular Structure and Dynamics

Inhibition of respiratory syncytial virus by Daclatasvir and its derivatives: synthesis of computational derivatives as a new drug development

Article

作者: Afreen, Shagufta ; Mitra, Debanjan ; Das Mohapatra, Pradeep K. ; Abdalla, Mohnad

The most common cause of respiratory tract illness in newborns and young children is the respiratory syncytial virus (RSV). There is no approved vaccination or specific antiviral medication for RSV infections. Here, an attempt has been made to explore the potential of currently marketed drugs as well as their probable derivatives to improve the possibility of developing stronger medications against RSV. From the 100 synthetic drug compounds library, the best drug molecule was identified through drug-likeness properties, toxicity, molecular docking and molecular dynamics simulations. Molecular Mechanics Generalized Born Surface Area (MM-GBSA) was also a method that was applied in this study. Daclatasvir showed the highest binding energy and appeared as the best drug to inhibit matrix protein and a fusion protein of RSV. Based on Daclatasvir, 40 computational derivatives were made. D28, D34 and D40 showed far better results than the actual drug. Changes in lipophilicity character increase the binding energy of derivatives. Molecular dynamic simulations showed their non-deviated, non-fluctuated and stable complex formation with target proteins. The high number of amino acid contacts throughout the trajectory increases the stability and effectiveness of derivatives. The key to producing a novel medicine to eradicate RSV is provided by derivatives. Daclatasvir will be employed as a potential RSV inhibitor up until that point.

2024-11-12·Proceedings of the National Academy of Sciences

Combatting melioidosis with chemical synthetic lethality

Article

作者: Gallant, Étienne ; Klaus, Jennifer R. ; Amaya Lopez, Cindy Y. ; Zhang, Yifan ; Chandler, Josephine R. ; Davis, Katherine M. ; Seyedsayamdost, Mohammad R. ; McWhorter, Kirklin L. ; Rosen, Paul C. ; Jhunjhunwala, Riddhi

Burkholderia thailandensis has emerged as a nonpathogenic surrogate for Burkholderia pseudomallei , the causative agent of melioidosis, and an important Gram-negative model bacterium for studying the biosynthesis and regulation of secondary metabolism. We recently reported that subinhibitory concentrations of trimethoprim induce vast changes in both the primary and secondary metabolome of B. thailandensis . In the current work, we show that the folate biosynthetic enzyme FolE2 is permissive under standard growth conditions but essential for B. thailandensis in the presence of subinhibitory doses of trimethoprim. Reasoning that FolE2 may serve as an attractive drug target, we screened for and identified ten inhibitors, including dehydrocostus lactone (DHL), parthenolide, and β-lapachone, all of which are innocuous individually but form a chemical-synthetic lethal combination with subinhibitory doses of trimethoprim. We show that DHL is a mechanism-based inhibitor of FolE2 and capture the structure of the covalently inhibited enzyme using X-ray crystallography. In vitro, the combination of subinhibitory trimethoprim and DHL is more potent than Bactrim, the current standard of care against melioidosis. Moreover, unlike Bactrim, this combination does not affect the growth of most commensal and beneficial gut bacteria tested, thereby providing a degree of specificity against B. pseudomallei . Our work provides a path for identifying antimicrobial drug targets and for utilizing binary combinations of molecules that form a toxic cocktail based on metabolic idiosyncrasies of specific pathogens.

2024-10-01·Journal of Biological Chemistry

Development of a high throughput cytochrome P450 ligand-binding assay

Article

作者: Scott, Emily E. ; Frydendall, Elyse K ; Frydendall, Elyse ; Scott, Emily E

Human cytochrome P450 enzymes are membrane-embedded monooxygenases responsible for xenobiotic metabolism, steroidogenesis, fatty acid metabolism, and vitamin metabolism. Their active sites can accommodate diverse small molecules and understanding these interactions is key to decoding enzymatic functionality and designing drugs. The most common method for characterizing small molecule binding is quantifying absorbance changes that typically occur when ligands enter the active site near the heme iron. Traditionally, such titrations are monitored by a spectrophotometer, requiring significant manual time, protein, and increasing solvents. This assay was adapted for semi-automated high throughput screening, increasing throughput 50-fold while requiring less protein and keeping solvent concentrations constant. This 384-well assay was validated for both type I and II shifts typically observed for substrates and heme-coordinating inhibitors, respectively. This assay was used to screen a library of ∼100 diverse imidazole-containing compounds which can coordinate with the heme iron if compatible with the overall active site. Three human cytochrome P450 enzymes were screened: drug-metabolizing CYP2A6 and CYP2D6 and sterol-metabolizing CYP8B1. Each bound different sets of imidazole compounds with varying K_d values, providing a unique binding fingerprint. As a final validation, the K_d values were used to generate pharmacophores to compare to experimental X-ray structures. Applications for the high-throughput assay include the following: 1) facilitating generation of pharmacophores for enzymes where structures are not available, 2) screening to identify ligands for P450 orphans, 3) screening for inhibitors of P450s drug targets, 4) screening potential new drugs to avoid and/or control P450 metabolism, and 5) efficient validation of computational ligand binding predictions.

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

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

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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)	鏇構憲選鑰選鬱壓鬱構(糧糧廠窪餘鹹憲鬱廠製) = 鬱獵願顧艱醖構繭鹹簾糧糧鬱膚憲簾繭觸簾構 (簾膚獵壓壓構蓋糧選鑰, 遞糧顧遞繭鹹積鬱夢網 ~ 築觸積餘獵蓋獵鹹願顧) 更多	-	2013-01-21
				Gynazole 1 vaginal cream (Reference Product)	鏇構憲選鑰選鬱壓鬱構(糧糧廠窪餘鹹憲鬱廠製) = 餘夢顧鑰築蓋鏇積願鹽糧糧鬱膚憲簾繭觸簾構 (簾膚獵壓壓構蓋糧選鑰, 齋餘窪憲觸獵範獵顧齋 ~ 積壓積築築壓夢獵獵鏇) 更多