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1
SCY-078, a Novel Fungicidal Agent, Demonstrates Distribution to Tissues Associated with Fungal Infections during Mass Balance Studies with Intravenous and Oral [C]SCY-078 in Albino and Pigmented Rats.在静脉内和口服 [C]SCY-078 于白化和色素沉着大鼠的体内物质平衡研究中,新型杀真菌剂 SCY-078 显示向与真菌感染相关的组织分布。
Antimicrob Agents Chemother. 2019 Jan 29;63(2). doi: 10.1128/AAC.02119-18. Print 2019 Feb.
2
Clinical Pharmacokinetics and Drug-Drug Interaction Potential for Coadministered SCY-078, an Oral Fungicidal Glucan Synthase Inhibitor, and Tacrolimus.SCY-078(一种口服抗真菌葡聚糖合成酶抑制剂)与他克莫司联合用药的临床药代动力学和药物相互作用潜力。
Clin Pharmacol Drug Dev. 2019 Jan;8(1):60-69. doi: 10.1002/cpdd.588. Epub 2018 Jun 27.
3
Lack of Impact by SCY-078, a First-in-Class Oral Fungicidal Glucan Synthase Inhibitor, on the Pharmacokinetics of Rosiglitazone, a Substrate for CYP450 2C8, Supports the Low Risk for Clinically Relevant Metabolic Drug-Drug Interactions.口服真菌葡聚糖合成酶抑制剂 SCY-078 对罗格列酮(CYP450 2C8 底物)药代动力学无影响,提示其发生临床相关代谢性药物相互作用的风险低。
J Clin Pharmacol. 2018 Oct;58(10):1305-1313. doi: 10.1002/jcph.1146. Epub 2018 May 10.
4
SCY-078 Is Fungicidal against Candida Species in Time-Kill Studies.在时间-杀菌研究中,SCY-078对念珠菌属具有杀菌作用。
Antimicrob Agents Chemother. 2017 Feb 23;61(3). doi: 10.1128/AAC.01961-16. Print 2017 Mar.
5
Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis.新型口服活性抗真菌葡聚糖合成抑制剂SCY-078在播散性念珠菌病小鼠模型中的临床前药代动力学和药效学靶点
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02068-16. Print 2017 Apr.
6
Ibrexafungerp: An orally active β-1,3-glucan synthesis inhibitor.依布硒康唑:一种口服活性的β-1,3-葡聚糖合成抑制剂。
Bioorg Med Chem Lett. 2021 Jan 15;32:127661. doi: 10.1016/j.bmcl.2020.127661. Epub 2020 Nov 4.
7
MSG-10: a Phase 2 study of oral ibrexafungerp (SCY-078) following initial echinocandin therapy in non-neutropenic patients with invasive candidiasis.MSG-10:在非中性粒细胞减少症侵袭性念珠菌病患者中,初始使用棘白菌素类药物治疗后的口服伊布列康唑(SCY-078)的 2 期研究。
J Antimicrob Chemother. 2019 Oct 1;74(10):3056-3062. doi: 10.1093/jac/dkz277.
8
Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model.使用体内小鼠侵袭性念珠菌病模型对新型口服葡聚糖合酶抑制剂SCY-078(MK-3118)进行药效学靶点评估。
Antimicrob Agents Chemother. 2015 Feb;59(2):1265-72. doi: 10.1128/AAC.04445-14. Epub 2014 Dec 15.
9
The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation.新兴病原体耳念珠菌:生长表型、毒力因子、抗真菌药物活性以及新型葡聚糖合成抑制剂SCY-078对生长形态和生物膜形成的影响
Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02396-16. Print 2017 May.
10
Oral glucan synthase inhibitor SCY-078 is effective in an experimental murine model of invasive candidiasis caused by WT and echinocandin-resistant Candida glabrata.口服葡聚糖合成酶抑制剂 SCY-078 对 WT 和棘白菌素耐药性光滑念珠菌引起的侵袭性念珠菌病的实验性小鼠模型有效。
J Antimicrob Chemother. 2018 Feb 1;73(2):448-451. doi: 10.1093/jac/dkx422.

引用本文的文献

1
Ibrexafungerp: A narrative overview.依布硒芬净:概述
Curr Res Microb Sci. 2024 May 27;6:100245. doi: 10.1016/j.crmicr.2024.100245. eCollection 2024.
2
Novel antifungals and treatment approaches to tackle resistance and improve outcomes of invasive fungal disease.新型抗真菌药物和治疗方法,以应对耐药性并改善侵袭性真菌感染的治疗结局。
Clin Microbiol Rev. 2024 Jun 13;37(2):e0007423. doi: 10.1128/cmr.00074-23. Epub 2024 Apr 11.
3
Antifungal resistance, combinations and pipeline: oh my!抗真菌耐药性、联合用药及研发进展:天哪!
Drugs Context. 2023 Nov 9;12. doi: 10.7573/dic.2023-7-1. eCollection 2023.
4
New Approaches to Manage Infections in Transplant Recipients: Report From the 2023 GTI (Infection and Transplantation Group) Annual Meeting.移植受者感染管理的新方法:来自2023年GTI(感染与移植小组)年会的报告。
Transpl Int. 2023 Nov 9;36:11859. doi: 10.3389/ti.2023.11859. eCollection 2023.
5
Headaches in a Horseback Rider.一名骑马者的头痛
Open Forum Infect Dis. 2023 Mar 20;10(3):ofad145. doi: 10.1093/ofid/ofad145. eCollection 2023 Mar.
6
Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis: Design, Development and Place in Therapy.伊布列康唑治疗外阴阴道念珠菌病:设计、研发及治疗定位。
Drug Des Devel Ther. 2023 Feb 7;17:363-367. doi: 10.2147/DDDT.S339349. eCollection 2023.
7
Ibrexafungerp, a Novel Triterpenoid Antifungal in Development for the Treatment of Mold Infections.依布康唑,一种正在研发用于治疗霉菌感染的新型三萜类抗真菌药物。
J Fungi (Basel). 2022 Oct 25;8(11):1121. doi: 10.3390/jof8111121.
8
Oral Ibrexafungerp for Vulvovaginal Candidiasis Treatment: An Analysis of VANISH 303 and VANISH 306.口服伊布利康唑治疗外阴阴道念珠菌病:VANISH 303 和 VANISH 306 分析。
J Womens Health (Larchmt). 2023 Feb;32(2):178-186. doi: 10.1089/jwh.2022.0132. Epub 2022 Oct 17.
9
The Menace of Epidemic Amidst the COVID-19 Pandemic: A Systematic Review.新冠疫情期间流行病的威胁:一项系统综述
Diseases. 2022 Aug 29;10(3):58. doi: 10.3390/diseases10030058.
10
Invasive candidiasis: investigational drugs in the clinical development pipeline and mechanisms of action.侵袭性念珠菌病:临床开发管道中的研究药物及作用机制。
Expert Opin Investig Drugs. 2022 Aug;31(8):795-812. doi: 10.1080/13543784.2022.2086120. Epub 2022 Jun 15.

本文引用的文献

1
Clinical Pharmacokinetics and Drug-Drug Interaction Potential for Coadministered SCY-078, an Oral Fungicidal Glucan Synthase Inhibitor, and Tacrolimus.SCY-078(一种口服抗真菌葡聚糖合成酶抑制剂)与他克莫司联合用药的临床药代动力学和药物相互作用潜力。
Clin Pharmacol Drug Dev. 2019 Jan;8(1):60-69. doi: 10.1002/cpdd.588. Epub 2018 Jun 27.
2
Differential Activity of the Oral Glucan Synthase Inhibitor SCY-078 against Wild-Type and Echinocandin-Resistant Strains of Candida Species.口服葡聚糖合酶抑制剂SCY-078对白色念珠菌野生型和棘白菌素耐药菌株的差异活性
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.00161-17. Print 2017 Aug.
3
Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis.新型口服活性抗真菌葡聚糖合成抑制剂SCY-078在播散性念珠菌病小鼠模型中的临床前药代动力学和药效学靶点
Antimicrob Agents Chemother. 2017 Mar 24;61(4). doi: 10.1128/AAC.02068-16. Print 2017 Apr.
4
SCY-078 Is Fungicidal against Candida Species in Time-Kill Studies.在时间-杀菌研究中,SCY-078对念珠菌属具有杀菌作用。
Antimicrob Agents Chemother. 2017 Feb 23;61(3). doi: 10.1128/AAC.01961-16. Print 2017 Mar.
5
Echinocandins: The Expanding Antifungal Armamentarium.棘白菌素类药物:不断扩展的抗真菌药物武器库。
Clin Infect Dis. 2015 Dec 1;61 Suppl 6:S604-11. doi: 10.1093/cid/civ814.
6
Pharmacodynamic target evaluation of a novel oral glucan synthase inhibitor, SCY-078 (MK-3118), using an in vivo murine invasive candidiasis model.使用体内小鼠侵袭性念珠菌病模型对新型口服葡聚糖合酶抑制剂SCY-078(MK-3118)进行药效学靶点评估。
Antimicrob Agents Chemother. 2015 Feb;59(2):1265-72. doi: 10.1128/AAC.04445-14. Epub 2014 Dec 15.
7
Tissue penetration of antifungal agents.抗真菌药物的组织穿透性。
Clin Microbiol Rev. 2014 Jan;27(1):68-88. doi: 10.1128/CMR.00046-13.
8
Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates.烟曲霉素衍生物 MK-3118 对临床棘白菌素耐药的念珠菌属和曲霉属分离株显示出体外活性增强。
Antimicrob Agents Chemother. 2014;58(2):1248-51. doi: 10.1128/AAC.02145-13. Epub 2013 Dec 9.
9
In vitro activity of a new oral glucan synthase inhibitor (MK-3118) tested against Aspergillus spp. by CLSI and EUCAST broth microdilution methods.CLSI 和 EUCAST 肉汤微量稀释法检测新型口服葡聚糖合成酶抑制剂(MK-3118)对曲霉菌属的体外活性。
Antimicrob Agents Chemother. 2013 Feb;57(2):1065-8. doi: 10.1128/AAC.01588-12. Epub 2012 Dec 10.
10
Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST).新型口服葡聚糖合成酶抑制剂 MK-3118 的活性,经两种国际方法(CLSI 和 EUCAST)检测对念珠菌属的作用。
J Antimicrob Chemother. 2013 Apr;68(4):858-63. doi: 10.1093/jac/dks466. Epub 2012 Nov 28.

在静脉内和口服 [C]SCY-078 于白化和色素沉着大鼠的体内物质平衡研究中,新型杀真菌剂 SCY-078 显示向与真菌感染相关的组织分布。

SCY-078, a Novel Fungicidal Agent, Demonstrates Distribution to Tissues Associated with Fungal Infections during Mass Balance Studies with Intravenous and Oral [C]SCY-078 in Albino and Pigmented Rats.

机构信息

SCYNEXIS, Inc., Jersey City, New Jersey, USA.

QPS, Newark, Delaware, USA.

出版信息

Antimicrob Agents Chemother. 2019 Jan 29;63(2). doi: 10.1128/AAC.02119-18. Print 2019 Feb.

DOI:10.1128/AAC.02119-18
PMID:30478166
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6355592/
Abstract

SCY-078, a fungicidal β-1,3-glucan synthesis inhibitor administered as intravenous or oral [C]SCY-078 to rats, was distributed primarily into tissues associated with invasive fungal disease (kidney, lung, liver, spleen, bone marrow, muscle, vaginal tissue, and skin) to levels exceeding those in plasma. Oral fraction absorbed was ∼40%. Elimination was primarily via bile and feces (∼90%) and urine (∼1.5%). Mean half-time was ∼8 h. Quantitative whole-body autoradiography showed a rapid distribution at 8 h and elimination by 168 h postdose.

摘要

SCY-078 是一种杀真菌的β-1,3-葡聚糖合成抑制剂,以静脉注射或口服[C]SCY-078 的形式给予大鼠,主要分布于与侵袭性真菌感染(肾脏、肺部、肝脏、脾脏、骨髓、肌肉、阴道组织和皮肤)相关的组织中,其水平超过血浆。口服吸收部分约为 40%。消除主要通过胆汁和粪便(约 90%)和尿液(约 1.5%)。平均半衰期约为 8 小时。定量全身放射自显影显示,在给药后 8 小时迅速分布,168 小时后消除。