研究性真菌Cyp51抑制剂VT-1129对新型隐球菌和格特隐球菌具有强大的体外活性。
The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii.
作者信息
Lockhart Shawn R, Fothergill Annette W, Iqbal Naureen, Bolden Carol B, Grossman Nina T, Garvey Edward P, Brand Stephen R, Hoekstra William J, Schotzinger Robert J, Ottinger Elizabeth, Patterson Thomas F, Wiederhold Nathan P
机构信息
Mycotic Diseases Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
出版信息
Antimicrob Agents Chemother. 2016 Mar 25;60(4):2528-31. doi: 10.1128/AAC.02770-15. Print 2016 Apr.
Abstract
Thein vitroactivities of the novel fungal Cyp51 inhibitor VT-1129 were evaluated against a large panel ofCryptococcus neoformansandCryptococcus gattiiisolates. VT-1129 demonstrated potent activities against bothCryptococcusspecies as demonstrated by low MIC50and MIC90values. ForC. gattii, thein vitropotency was maintained against all genotypes. In addition, significantly lower geometric mean MICs were observed for VT-1129 than for fluconazole againstC. neoformans, including isolates with reduced fluconazole susceptibility.
摘要
新型真菌Cyp51抑制剂VT-1129的体外活性针对大量新型隐球菌和格特隐球菌分离株进行了评估。VT-1129对这两种隐球菌均显示出强效活性，其MIC50和MIC90值较低即证明了这一点。对于格特隐球菌，其体外活性对所有基因型均保持有效。此外，观察到VT-1129针对新型隐球菌的几何平均MIC显著低于氟康唑，包括对氟康唑敏感性降低的分离株。
相似文献
1
The Investigational Fungal Cyp51 Inhibitor VT-1129 Demonstrates Potent In Vitro Activity against Cryptococcus neoformans and Cryptococcus gattii.研究性真菌Cyp51抑制剂VT-1129对新型隐球菌和格特隐球菌具有强大的体外活性。
Antimicrob Agents Chemother. 2016 Mar 25;60(4):2528-31. doi: 10.1128/AAC.02770-15. Print 2016 Apr.
2
Azole resistance in Cryptococcus gattii from the Pacific Northwest: Investigation of the role of ERG11.西北太平洋地区新型隐球菌唑类耐药性研究：ERG11 作用的研究
Antimicrob Agents Chemother. 2013 Nov;57(11):5478-85. doi: 10.1128/AAC.02287-12. Epub 2013 Aug 26.
3
The Fungal Cyp51 Inhibitor VT-1129 Is Efficacious in an Experimental Model of Cryptococcal Meningitis.真菌细胞色素 P450 抑制剂 VT-1129 在新型隐球菌性脑膜炎实验模型中具有疗效。
Antimicrob Agents Chemother. 2018 Aug 27;62(9). doi: 10.1128/AAC.01071-18. Print 2018 Sep.
4
Reduced Susceptibility to Azoles in Cryptococcus gattii Correlates with the Substitution R258L in a Substrate Recognition Site of the Lanosterol 14-α-Demethylase.隐球菌中唑类药物敏感性降低与 14α-羊毛甾醇去甲基酶底物识别位点的 R258L 取代有关。
Microbiol Spectr. 2023 Aug 17;11(4):e0140323. doi: 10.1128/spectrum.01403-23. Epub 2023 Jun 21.
5
Activity of VT-1129 against Cryptococcus neoformans clinical isolates with high fluconazole MICs.VT-1129对氟康唑最低抑菌浓度较高的新型隐球菌临床分离株的活性。
Med Mycol. 2017 Jun 1;55(4):453-456. doi: 10.1093/mmy/myw089.
6
Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models.在小鼠感染模型中评估VT-1161治疗球孢子菌病的效果。
Antimicrob Agents Chemother. 2015 Dec;59(12):7249-54. doi: 10.1128/AAC.00593-15. Epub 2015 Sep 14.
7
Molecular epidemiology and in vitro antifungal susceptibility testing of 108 clinical Cryptococcus neoformans sensu lato and Cryptococcus gattii sensu lato isolates from Denmark.对来自丹麦的108株新型隐球菌复合体和格特隐球菌复合体临床分离株进行的分子流行病学及体外抗真菌药敏试验
Mycoses. 2016 Sep;59(9):576-84. doi: 10.1111/myc.12507. Epub 2016 Apr 8.
8
Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity.新型候选研究药物VT-1598与烟曲霉甾醇14α-脱甲基酶复合物的晶体结构为其广谱抗真菌活性提供了见解。
Antimicrob Agents Chemother. 2017 Jun 27;61(7). doi: 10.1128/AAC.00570-17. Print 2017 Jul.
9
Activities of the Novel Investigational Tetrazoles VT-1161 and VT-1598 Compared to the Triazole Antifungals against Azole-Resistant Strains and Clinical Isolates of .新型研究四唑 VT-1161 和 VT-1598 对唑类耐药株和临床分离株的活性比较。
Antimicrob Agents Chemother. 2019 May 24;63(6). doi: 10.1128/AAC.00341-19. Print 2019 Jun.
10
Identification of a Cryptococcus neoformans cytochrome P450 lanosterol 14α-demethylase (Erg11) residue critical for differential susceptibility between fluconazole/voriconazole and itraconazole/posaconazole.鉴定出新型隐球菌细胞色素 P450 羊毛甾醇 14α-脱甲基酶（Erg11）中一个关键残基，该残基决定了氟康唑/伏立康唑与伊曲康唑/泊沙康唑之间的差异敏感性。
Antimicrob Agents Chemother. 2012 Mar;56(3):1162-9. doi: 10.1128/AAC.05502-11. Epub 2011 Dec 12.
引用本文的文献
1
Next-generation antifungal drugs: Mechanisms, efficacy, and clinical prospects.新一代抗真菌药物：作用机制、疗效及临床前景。
Acta Pharm Sin B. 2025 Aug;15(8):3852-3887. doi: 10.1016/j.apsb.2025.06.013. Epub 2025 Jun 23.
2
Targeting fungal lipid synthesis for antifungal drug development and potentiation of contemporary antifungals.以真菌脂质合成作为抗真菌药物研发及增强现有抗真菌药物效果的靶点。
NPJ Antimicrob Resist. 2025 Apr 12;3(1):27. doi: 10.1038/s44259-025-00093-4.
3
Assessment of the potential risk of oteseconazole and two other tetrazole antifungals to inhibit adrenal steroidogenesis and peripheral metabolism of corticosteroids.评估奥替康唑和其他两种四氮唑类抗真菌药抑制肾上腺类固醇生成及皮质类固醇外周代谢的潜在风险。
Front Pharmacol. 2024 Aug 8;15:1394846. doi: 10.3389/fphar.2024.1394846. eCollection 2024.
4
Antifungals: From Pharmacokinetics to Clinical Practice.抗真菌药物：从药代动力学到临床实践
Antibiotics (Basel). 2023 May 9;12(5):884. doi: 10.3390/antibiotics12050884.
5
Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review.控制人类抗真菌耐药性风险的潜在策略：全面综述
Antibiotics (Basel). 2023 Mar 18;12(3):608. doi: 10.3390/antibiotics12030608.
6
Exploring CYP51 and Its Cognate Reductase as a Drug Target.探索CYP51及其同源还原酶作为药物靶点
J Fungi (Basel). 2022 Nov 28;8(12):1256. doi: 10.3390/jof8121256.
7
New Antifungal Agents with Azole Moieties.含唑类基团的新型抗真菌药物
Pharmaceuticals (Basel). 2022 Nov 17;15(11):1427. doi: 10.3390/ph15111427.
8
Pulmonary Cryptococcosis.肺隐球菌病
J Fungi (Basel). 2022 Oct 31;8(11):1156. doi: 10.3390/jof8111156.
9
Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents.新型抗真菌药物的药效学、作用机制与耐药性以及活性谱
J Fungi (Basel). 2022 Aug 16;8(8):857. doi: 10.3390/jof8080857.
10
In Silico Structural Modeling and Analysis of Interactions of Cytochrome P450 Monooxygenases CYP51s with Substrates and Azoles.计算机模拟结构建模与细胞色素 P450 单加氧酶 CYP51 与底物和唑类药物相互作用分析。
Int J Mol Sci. 2021 Jul 22;22(15):7811. doi: 10.3390/ijms22157811.
本文引用的文献
1
The clinical candidate VT-1161 is a highly potent inhibitor of Candida albicans CYP51 but fails to bind the human enzyme.临床候选药物VT-1161是白色念珠菌CYP51的高效抑制剂，但无法与人源酶结合。
Antimicrob Agents Chemother. 2014 Dec;58(12):7121-7. doi: 10.1128/AAC.03707-14. Epub 2014 Sep 15.
2
Design and optimization of highly-selective fungal CYP51 inhibitors.高选择性真菌CYP51抑制剂的设计与优化
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3455-8. doi: 10.1016/j.bmcl.2014.05.068. Epub 2014 Jun 9.
3
Epidemiologic cutoff values for triazole drugs in Cryptococcus gattii: correlation of molecular type and in vitro susceptibility.隐球菌中三唑类药物的流行病学截断值：分子类型与体外药敏的相关性。
Diagn Microbiol Infect Dis. 2012 Jun;73(2):144-8. doi: 10.1016/j.diagmicrobio.2012.02.018. Epub 2012 Apr 10.
4
Trends in antifungal drug susceptibility of Cryptococcus neoformans isolates obtained through population-based surveillance in South Africa in 2002-2003 and 2007-2008.2002-2003 年和 2007-2008 年南非基于人群的监测中获得的新型隐球菌分离株的抗真菌药物敏感性趋势。
Antimicrob Agents Chemother. 2011 Jun;55(6):2606-11. doi: 10.1128/AAC.00048-11. Epub 2011 Mar 28.
5
In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental Cryptococcus gattii isolates.对全球范围内 350 株临床、兽医和环境分离的隐球菌的体外抗真菌药敏试验和扩增片段长度多态性基因分型研究。
Antimicrob Agents Chemother. 2010 Dec;54(12):5139-45. doi: 10.1128/AAC.00746-10. Epub 2010 Sep 20.
6
Cryptococcus.隐球菌。
Proc Am Thorac Soc. 2010 May;7(3):186-96. doi: 10.1513/pats.200907-063AL.
7
Antifungal susceptibility, serotyping, and genotyping of clinical Cryptococcus neoformans isolates collected during 18 years in a single institution in Madrid, Spain.西班牙马德里一家单家医疗机构 18 年间收集的临床新型隐球菌分离株的抗真菌药敏性、血清型和基因分型。
Med Mycol. 2010 Nov;48(7):942-8. doi: 10.3109/13693781003690067.
8
Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america.《隐球菌病治疗指南：美国传染病学会 2010 年更新版》
Clin Infect Dis. 2010 Feb 1;50(3):291-322. doi: 10.1086/649858.
9
Correlation of genotype and in vitro susceptibilities of Cryptococcus gattii strains from the Pacific Northwest of the United States.美国太平洋西北地区新型隐球菌分离株基因型与体外药敏相关性研究。
J Clin Microbiol. 2010 Feb;48(2):539-44. doi: 10.1128/JCM.01505-09. Epub 2009 Dec 9.
10
Consensus multi-locus sequence typing scheme for Cryptococcus neoformans and Cryptococcus gattii.新型隐球菌和格特隐球菌共识多位点序列分型方案。
Med Mycol. 2009;47(6):561-70. doi: 10.1080/13693780902953886.
Zotero 插件