更新于：2024-11-01

CYP51 (Yeast)

更新于：2024-11-01

基本信息

别名

CYP51 (Yeast)、CYPLI、Cytochrome P450 51

+ [2]

简介

Sterol 14alpha-demethylase that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions (PubMed:369554, PubMed:105731). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (PubMed:32679672). Starting from lanosterol (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of the sterol in the form of formate, and converts the sterol to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol biosynthesis (PubMed:369554, PubMed:105731, PubMed:3543000). Can demethylate susbtrates not intrinsic to yeast, such as eburicol (24-methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-cholestadien-3beta-ol (PubMed:3543000, PubMed:1872829).

关联

项与 CYP51 (Yeast) 相关的药物

CYP51 inhibitors-4j(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CYP51 inhibitors-4b(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CYP51 inhibitors-6f(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CYP51 (Yeast) 相关的临床结果

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100 项与 CYP51 (Yeast) 相关的转化医学

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0 项与 CYP51 (Yeast) 相关的专利（医药）

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392

项与 CYP51 (Yeast) 相关的文献（医药）

2024-09-16·Future Medicinal Chemistry

Design, synthesis, docking studies and bioactivity evaluation of 1,2,3-triazole eugenol derivatives

Article

作者: Scherer, Rodrigo ; Junker, Jochen ; de Sousa Cutrim, Thiago Antonio ; Teixeira, Róbson Ricardo ; Costa, Adilson Vidal ; Barcelos, Fernando Fontes ; do Nascimento, Cláudia Jorge ; Bezerra Morais, Pedro Alves ; Moreira, Luiza Carvalheira ; Rodrigues Gazolla, Poliana Aparecida ; Almeida Lima, Ângela Maria ; de Queiroz, Vagner Tebaldi ; Meireles, Leandra Martins ; Fronza, Marcio ; Almeida Barbosa, Luiz Cláudio

Aim: The design, synthesis, docking studies and evaluation of the in vitro antifungal and cytotoxic properties of eugenol (EUG) containing 1,2,3-triazole derivatives are reported. Most of the derivatives have not been reported.Materials & methods: The EUG derivatives were synthesized, molecular docked and tested for their antifungal activity.Results: The compounds showed potent antifungal activity against Trichophyton rubrum, associated with dermatophytosis. Compounds 2a and 2i exhibited promising results, with 2a being four-times more potent than EUG. The binding mode prediction was similar to itraconazole in the lanosterol-14-α-demethylase wild-type and G73E mutant binding sites. Additionally, the pharmacokinetic profile prediction suggests good gastrointestinal absorption and potential oral administration.Conclusion: Compound 2a is a promising antifungal agent against dermatophytosis caused by T. rubrum.

2024-08-12·Journal of Biomolecular Structure and Dynamics

Elucidation of furanone as ergosterol pathway inhibitor in Cryptococcus neoformans

Article

作者: Ramakrishnan, Jayapradha ; Mohan, Suma ; Sathiyamoorthy, Jananishree ; Uma Maheshwari, C ; Rathore, Sudarshan Singh

In the era of antiretroviral therapy, the prevalence of Cryptococcal infection among HIV patients in developed countries has decreased considerably. However, C. neoformans ranks top among the critical priority pathogen that affects a wide range of immunocompromised individuals. The threat of C. neoformans is because of its incredibly multifaceted intracellular survival capabilities. Cell membrane sterols especially ergosterol and enzymes of its biosynthetic pathway are considered fascinating drug targets because of their structural stability. In this study, the ergosterol biosynthetic enzymes were modeled and docked with furanone derivatives. Among the tested ligands Compound 6 has shown a potential interaction with Lanosterol 14 α-demethylase. This best-docked protein-ligand complex was taken further to molecular dynamics simulation. In addition, Compound 6 was synthesized and an in vitro study was conducted to quantify the ergosterol in Compound 6 treated cells. Altogether the computational and in vitro study demonstrates that Compound 6 has anticryptococcal activity by targeting the biosynthetic pathway of ergosterol.Communicated by Ramaswamy H. Sarma.

2024-08-01·Heliyon

Erythromycin-metal complexes: One-step synthesis, molecular docking analysis and antibacterial proficiency against pathogenic strains

Article

作者: Habib, Atiya ; Abah, Lian Ojotule ; Ali, Irfan ; Egu, Samuel Attah ; Idih, Sunday Okpanachi ; Omale, Aminu ; Michael, Ojochide Charity ; Omale, Jamila Audu ; Adaji, Mohammed Umar ; Onoja, Alexander David ; Edegbo, Emmanuel ; Hussaini, Jumai Zainab ; Qureshi, Urooj ; Achimugu, Lawrence

The study focused on the extraction of free erythromycin from commercially manufactured tablets and the use of metal salts to synthesize erythromycin-metal complexes, specifically involving silver (Ag), nickel (Ni), cobalt (Co), and copper (Cu). The synthesis was confirmed through various methods, including elemental analysis, thermogravimetric analysis, Fourier-transform infrared (FTIR), and UV-visible spectroscopy. The microbiological investigation involved Salmonella typhi, Escherichia coli, Staphylococcus aureus, Bacillus cereus, Candida albicans, and Microsporum canis as test organisms. The NCCLS broth microdilution reference method was used to determine the minimum fungicidal concentration and minimum inhibitory concentration of the complexes. The synthesized complexes were highly effective against a variety of fungi and bacteria, with compound Ery-Cu having MIC as low as 1.56 mg/mL, Ery-Cu and Ery-Ni with MBCs of 6.25 mg/mL and Ery-Cu having MFC of 6.25 mg/mL. Dose-dependent inhibitory effects were found upon examination of the antimicrobial susceptibility of specific complexes (Cu, Ni, Co and Ag) at varying concentrations of 100, 50, 25 and 12.5 mm/mL. Antibiotic susceptibility testing revealed efficacy against the tested pathogens. The study suggests that the synthesis of erythromycin-metal complexes, coupled with their antibacterial effectiveness against a diverse spectrum of bacteria and fungi, as they showed promising inhibitory properties when tested against a range of test species (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella typhi, Candida albicans, and Microsporum canis), could lead to the development of innovative antibacterial agents. Molecular docking simulations were used to examine the interactions between metal complexes with proteins filamentous temperature-sensitive protein Z and lanosterol 14α-demethylase. The study highlights the need for further exploration in pharmaceutical research.

项与 CYP51 (Yeast) 相关的新闻（医药）

2022-01-06

·Insight数据库

恒瑞 1 类抗真菌新药 SHR8008 上市申请获受理

1 月 5 日，CDE 官网显示，恒瑞医药进口 1 类新药 SHR8008 胶囊上市申请获受理。这是一款抗真菌药，用于治疗急性外阴阴道假丝酵母菌病。此前在 2021 年 11 月，恒瑞宣布其随机、双盲双模拟、氟康唑平行对照、多中心 III 期临床研究（SHR8008-302）主要研究终点结果达到方案预设的优效标准，SHR8008 治疗急性外阴阴道假丝酵母菌病痊愈率显著优于氟康唑。 SHR8008（oteseconazole）是一种新型口服唑类抗真菌药物，可高度特异性抑制真菌 CYP51 酶。恒瑞在 2019 年 6 月与 Mycovia 公司达成合作获得了这款药物的大中华区权益，交易总额超过 1 亿美元，包括 750 万美元研发付款（分别在 8 个季度平均支付） + 不超过 900 万美元中国研发里程碑款 + 累计不超过 9200 万美元的基于净销售额的销售里程碑款，同时以 7% 至 11% 的比例向 Mycovia 公司支付销售提成。在美国，Mycovia 公司已经完成针对急性外阴阴道假丝酵母菌病的临床 II 期研究和 1 项针对复发性外阴阴道念珠菌病的临床 III 期研究，2021 年 7 月向美国 FDA 递交了新药上市申请（NDA），并被纳入优先审评审批，PDUFA 日期在 2022 年 1 月 27 日，也是获批在望。外阴阴道假丝酵母菌病（VVC）是育龄女性的常见病和多发病，也被称为霉菌性阴道炎、外阴阴道念珠菌病。大约 75% 的女性一生中都会患一次 VVC，40%~50% 会再次发病。VVC 反复发作、难以根治的特点已经严重影响患者的生活质量。然而，现有标准治疗药物氟康唑对 VVC 的疗效有限，耐药性和安全性风险不容忽视，临床治疗需求未被满足。恒瑞在中国递交上市申请是基于 SHR8008-302 研究，这是一项评价 SHR8008 胶囊治疗急性外阴阴道假丝酵母菌病的有效性与安全性的随机、双盲双模拟、氟康唑平行对照、多中心 III 期临床研究，由北京清华长庚医院廖秦平教授担任主要研究者，全国 25 家中心共同参与，共入组 322 例急性外阴阴道假丝酵母菌病受试者。主要研究终点是第 28 天访视时急性外阴阴道假丝酵母菌病发作痊愈（定义为急性外阴阴道假丝酵母菌病症状体征消失同时真菌培养假丝酵母菌阴性）的受试者比例。截至 2021 年 11 月 4 日，恒瑞在该项目中共计投入 8939 万元。恒瑞在 2021 Q4 接连公布了 4 款新药达到注册临床研究主要终点、进入 pre-NDA 阶段的信息，除本次申报的 SHR8008 之外，另外 3 款新药分别是：PD-L1 单抗 SHR-1316、干眼病新药 SHR8058 滴眼液、镇痛药 SHR8554。除此之外，在 2021 年最后一天，恒瑞还收获了 1 类新药双黄蛋：SGLT-2 抑制剂恒格列净、CDK4/6 抑制剂达尔西利同时获批上市。如今恒瑞的创新药获批数量已经达到了 10 个，另有 3 款新药处于上市申请中，除了本次申报上市的 SHR8008，还包括 DPP4 抑制剂瑞格列汀、二代 AR 拮抗剂 SHR3680。尽管从竞争格局来看，这些新药几乎都面临着不小的压力，但创新药不断开花结果，向上市流程推进，无疑是抵消仿制药集采等负面因素的重要途径。参考来源： 1、江苏恒瑞医药股份有限公司关于引进美国 Mycovia 公司产品的公告（公告编号：临 2019-044）； 2、Mycovia Pharmaceuticals Announces U.S. FDA Acceptance and Priority Review of New Drug Application for Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis | Businesswire

免疫疗法创新药优先审批抗体