更新于：2024-11-01

Ergosterol x SQLE

更新于：2024-11-01

基本信息

关联

项与 Ergosterol x SQLE 相关的药物

Amorolfine Hydrochloride

盐酸阿莫罗芬

靶点

Ergosterol x SQLE

作用机制

麦角固醇生物合成抑制剂 [+1]

在研机构

Galderma Holding SA [+3]

原研机构

Teika Pharmaceutical Co., Ltd.

在研适应症

真菌病 [+5]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1993-10-01

项与 Ergosterol x SQLE 相关的临床试验

ChiCTR2300074178 / SuspendedIIT

Q-switched Nd:YAG laser versus Amorolfine Hydrochloride Cream in treatment of Distal lateral subungual onychomycosis in older adults

开始日期2023-08-01

申办/合作机构-

NCT05482763 / Active, not recruitingN/AIIT

Pilot Study on the Evaluation of the Efficacy, Tolerability and Safety of Topical and Oral Antifungals in the Treatment of Onychomycosis and Creation of a Library of Dermatological Clinical Isolates

This pilot, prospective, observational drug study aims to evaluate the efficacy, tolerability and safety of topical and oral antifungals in the treatment of onychomycosis caused by yeasts, dermatophytic moulds and non-dermatophytic moulds as well as correlate the scores in the MALDI-TOF method for the 'identification of genus and species of higher fungi utilizing the comparison between identification in direct optical microscopy, culture examination and optical microscopy and macroscopic and onychoscopic clinical aspects. Furthermore, an optional substudy will evaluate the drug resistance of clinical isolates using molecular or genetic methods.

开始日期2022-07-20

申办/合作机构

Università degli Studi di Roma Tor Vergata

100 项与 Ergosterol x SQLE 相关的临床结果

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100 项与 Ergosterol x SQLE 相关的转化医学

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0 项与 Ergosterol x SQLE 相关的专利（医药）

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项与 Ergosterol x SQLE 相关的文献（医药）

2021-01-01·Journal of Biological Chemistry2区 · 生物学

Deubiquitinase Ubp3 enhances the proteasomal degradation of key enzymes in sterol homeostasis

2区 · 生物学

Article

作者: Zhao, Zhenwen ; Lan, Qiuyan ; Deng, Zixin ; Wang, Yihao ; Li, Yanchang ; Xu, Ping ; Gao, Yuan ; He, Fuchu ; Lu, Hui ; Wang, Fuqiang ; Wu, Junzhu ; Li, Zhaodi

Sterol homeostasis is tightly controlled by molecules that are highly conserved from yeast to humans, the dysregulation of which plays critical roles in the development of antifungal resistance and various cardiovascular diseases. Previous studies have shown that sterol homeostasis is regulated by the ubiquitin-proteasome system. Two E3 ubiquitin ligases, Hrd1 and Doa10, are known to mediate the proteasomal degradation of 3-hydroxy-3-methylglutaryl-CoA reductase Hmg2 and squalene epoxidase Erg1 with accumulation of the toxic sterols in cells, but the deubiquitinases (DUBs) involved are unclear. Here, we screened for DUBs responsible for sterol homeostasis using yeast strains from a DUB-deletion library. The defective growth observed in ubp3-deleted (ubp3Δ) yeast upon fluconazole treatment suggests that lack of Ubp3 disrupts sterol homeostasis. Deep-coverage quantitative proteomics reveals that ergosterol biosynthesis is rerouted into a sterol pathway that generates toxic products in the absence of Ubp3. Further genetic and biochemical analysis indicated that Ubp3 enhances the proteasome's ability to degrade the ergosterol biosynthetic enzymes Erg1 and Erg3. The retardation of ergosterol enzyme degradation in the ubp3Δ strain resulted in the severe accumulation of the intermediate lanosterol and a branched toxic sterol, and ultimately disrupted sterol homeostasis and led to the fluconazole susceptibility. Our findings uncover a role for Ubp3 in sterol homeostasis and highlight its potential as a new antifungal target.

2020-11-01·Mycoses2区 · 医学

Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance

2区 · 医学

Article

作者: Elsner, Peter ; Wiegand, Cornelia ; Verma, Shyam B. ; Nenoff, Pietro ; Uhrlaß, Silke ; Singal, Archana ; Burmester, Anke ; Hipler, Uta‐Christina

SummaryBackgroundThe Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis.ObjectivesIllumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population.MethodsGrowth in fluconazole or terbinafine containing medium was analysed using a microplate‐laser‐nephelometry (MLN)‐based growth assay.ResultsAla 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance.ConclusionThe new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.

2020-01-01·Evidence-Based Complementary and Alternative Medicine4区 · 医学

Ellagic Acid Inhibits Trichophyton rubrum Growth via Affecting Ergosterol Biosynthesis and Apoptotic Induction

4区 · 医学

ArticleOA

作者: Abulizi, Abudumijiti ; Li, Zhi-Jian ; Huo, Shi-Xia ; Dou, Qin ; Abudouaini, Abudoujilili ; Abula, Amima ; Maimaiti, Youlidouzi ; Wang, Chun ; Aibai, Silafu

Background. Trichophyton rubrum, among other dermatophytes, is a major causative agent for superficial dermatomycoses like onychomycosis and tinea pedis, especially among pediatric and geriatric populations. Ellagic acid (EA) and shikonin (SK) have been reported to have many bioactivities, including antifungal activity. However, the mechanism of EA and SK on Trichophyton rubrum has not yet been reported. Objectives. The purposes of this study were to evaluate the antifungal activities of EA and SK against Trichophyton rubrum and to illuminate the underlying action mechanisms. Methods. The effect of EA (64, 128, and 256 μg/mL) and SK (8, 4, and 2 μg/mL) on Trichophyton rubrum was investigated with different doses via detecting cell viability, ultrastructure with using a scanning electron microscope (SEM), cell apoptosis and necrosis by using the flow cytometry instrument technique (FCIT), and the ergosterol biosynthesis pathway‐related fungal cell membrane key gene expressions in vitro. Results. SEM detection revealed that the T. rubrum cell surface was shrivelled, folded, and showed deformation and expansion, visible surface peeling, and broken hyphae, and cell contents overflowed after being treated with EA and SK; the cell apoptosis rate was significantly increased in dose‐dependent manner after T. rubrum was treated with EA and SK; the qPCR results showed that mRNA expression of MEP4 and SUB1 was downregulated in EA‐ and SK‐treated groups. Conclusions. Overall, our results revealed the underlying antifungal mechanism of EA and SK, which may be related to the destruction of the fungal cell membrane and inhibition of C14 demethylase and the catalytic rate of squalene cyclooxidase in the ergosterol biosynthesis pathway via downregulation of MEP4 and SUB1, suggesting that EA and SK have the potential to be developed further as a natural antifungal agent for clinical use.