Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir(Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir) - 药物靶点：NS3/NS4A x NS5A x NS5B polymerase_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Grazoprevir/MK-3682/MK-8408、Grazoprevir/MK-3682/ruzasvir、Grazoprevir/ruzasvir/MK-3682

+ [8]

靶点

NS3/NS4A x NS5A x NS5B polymerase

作用方式

抑制剂

作用机制

NS3/NS4A抑制剂(丙型肝炎病毒NS3/NS4A丝氨酸蛋白酶抑制剂)、NS5A抑制剂(非结构蛋白5A抑制剂)、NS5B polymerase抑制剂(丙型肝炎病毒NS5B RNA依赖的RNA聚合酶抑制剂)

治疗领域

感染消化系统疾病

在研适应症-

非在研适应症

丙型肝炎慢性丙型肝炎

原研机构

Merck & Co., Inc.

在研机构-

非在研机构

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLCMerck GmbH

最高研发阶段终止临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C22H29ClN3O9P

InChIKeySFPFZQKYPOWCSI-KHFYHRBSSA-N

CAS号1496551-77-9

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关联

4

项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的临床试验

NCT02661126

/ Completed临床1期

A Two-Part, Open-Label Study to Investigate the Single-Dose Pharmacokinetics of MK-3682B (MK-3682/MK-5172/MK-8408 Fixed Dose Combination) When Administered to Subjects With Moderate and Severe Renal Insufficiency

The purpose of this study is to compare the plasma pharmacokinetics (PK) of single doses of MK-3682B, a fixed dose combination (FDC) tablet containing uprifosbuvir (MK-3682) + grazoprevir (MK-5172) + ruzasvir (MK-8408) in participants with moderate (Part 1) and severe (Part 2) renal insufficiency (RI) to plasma PK in healthy participants.

开始日期2016-01-19

申办/合作机构

Merck Sharp & Dohme Corp.

NCT02613403

/ Terminated临床2期

A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682B (MK-5172 + MK-3682 + MK-8408 Fixed Dose Combination (FDC)) in Subjects With Chronic HCV GT1 or GT3 Infection Who Have Failed a Direct Acting Antiviral Regimen

This is a randomized, multicenter, 2-part, open-label trial of the combination regimen of grazoprevir (GZR [MK-5172]; 100mg), uprifosbuvir (UPR [MK-3682]; 450 mg) and ruzasvir (RZR [MK-8408]; 60 mg) with and without Ribavirin (RBV) in cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) previously failing a direct-acting antiviral regimen (DAA). The combination regimen, referred to as MK-3682B, will be administered as two fixed-dose combination (FDC) tablets, given once-daily. The study will evaluate the efficacy of MK-3682B with or without RBV as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy.

开始日期2015-12-10

申办/合作机构

Merck Sharp & Dohme LLC

NCT02332720

/ Completed临床2期

A Phase II, Randomized, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-5172 and MK-3682 With Either MK-8742 or MK-8408 in Subjects With Chronic HCV GT3, GT4, GT5, and GT6 Infection

This is a randomized, three-part, parallel-group, open-label trial of grazoprevir (MK-5172) (100 mg) and uprifosbuvir (MK-3682) (300 mg or 450 mg) with either elbasvir (MK-8742) (50 mg) or ruzasvir (MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naive (TN) or treatment-experienced (TE) cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) genotype (GT) 3, GT4, GT5, or GT6. Part A will consist of 4 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir (MK-3682B) fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of uprifosbuvir (+) grazoprevir (+) ruzasvir with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).

开始日期2015-01-28

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的临床结果

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100 项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的转化医学

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100 项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的专利（医药）

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22

项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的文献（医药）

2024-11-01·Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Advancing optoelectronic characteristics of Diketopyrrolopyrrole-Based molecules as donors for organic and as hole transporting materials for perovskite solar cells

Article

作者: Lim, Jongchul ; Adnan, Muhammad ; Hussain, Riaz ; Darwish, Hany W ; Irshad, Zobia ; Kashif, Muhammad

A stable and efficient hole-transport material (HTM) is crucial for high-performance perovskite solar cells (PSCs). A 2,2',7,7'-tetrakis[N,N-di(4-methoxyphenyl)amino]-9,9'-spirobifluorene (Spiro-MeOTAD) being used widely to prepare highly efficient PSCs. However, Spiro-MeOTAD has some limitations due to its complex synthesis, which increases its cost, and it also requires dopants to improve its performance. Therefore, we designed thirteen unique small-molecule-based HTMs (MK1-MK13), which are easy to synthesize, highly cost-effective, and don't require dopants to prepare efficient PSCs. Their electrical and optical properties are then investigated theoretically using advanced quantum chemical approaches. The designed molecules showed lower energy gaps and improved optical and optoelectronic characteristics because of the improved phase inversion geometry. The detailed photo-physical and optoelectronic characteristics have been studied using density functional theory (DFT) and time-dependent (TD-DFT) calculations. Moreover, we investigated the impact of holes and electrons and the density of states, open-circuit voltage, frontier molecular orbital, transition density matrix, and other structural and photovoltaic characteristics of these materials. Among these, the MK3 molecule possesses the much narrower optical band gap of 1.04 eV and absorbance (λ _max) of 684 nm, respectively. In addition, a profound investigation of the MK3/PC₆₁BM blend shows excellent charge transfer at the acceptor-donor interface. Therefore, our proposed technique is necessary for generating appropriate photovoltaic materials for efficient optoelectronic devices and is helpful in further advancing the field.

2018-11-30·ACS Omega3区 · 化学

Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives

3区 · 化学

ArticleOA

作者: Koehn, Jordan T ; Crick, Dean C ; Crans, Debbie C

Menaquinones (MKs) contain both a redox active quinone moiety and a hydrophobic repeating isoprenyl side chain of varying lengths and degrees of saturation. This characteristic structure allows MKs to play a key role in the respiratory electron transport system of some prokaryotes by shuttling electrons and protons between membrane-bound protein complexes, which act as electron acceptors and donors. Hydrophobic MK molecules with partially and fully saturated isoprenyl side chains are found in a wide range of eubacteria and archaea, and the structural variations of the MK analogues are evolutionarily conserved but poorly understood. For example, Mycobacterium tuberculosis, the causative agent of tuberculosis, uses predominantly MK-9(II-H₂) (saturated at the second isoprene unit) as its electron carrier and depends on the synthesis of MK-9(II-H₂) for survival in host macrophages. Thus, MKs with partially saturated isoprenyl side chains may represent a novel virulence factor. Naturally occurring longer MKs are very hydrophobic, whereas MK analogues that have a truncated (i.e., one to three isoprenes) isoprenyl side chain are less hydrophobic. This improves their solubility in aqueous solutions, allowing rigorous study of their structure and biological activity. We present the synthesis and characterization of two partially saturated MK analogues, MK-2(II-H₂) and MK-3(II-H₂), and two novel fully saturated MK derivatives, MK-2(I,II-H₄) and MK-3(I,II,III-H₆).

2018-01-25·Sheng wu gong cheng xue bao = Chinese journal of biotechnology

[Synthesis of vitamin K2 by isopentenyl transferase NovA in Pichia pastoris Gpn12].

Article

作者: Zhao, Genhai ; Wu, Xihua ; Sun, Xiaowen ; Li, Zhemin ; Fang, Xue ; Liu, Hui ; Ni, Wenfeng ; Wang, Peng ; Yang, Qiang ; Zheng, Zhiming ; Wang, Li

对异戊烯基转移酶NovQ 在毕赤酵母Gpn12 异源表达过程中诱导剂甲醇添加量进行了探究，并以毕赤酵母Gpn12 全细胞为酶源，以甲萘醌、异戊烯醇为前体，催化合成维生素K2 (MK-3)。每24 h 添加2%甲醇时，NovQ表达量提高约36%。考察摇瓶中初始pH、温度、甲醇添加量、前体 (甲萘醌、异戊烯醇) 添加量、催化时间、十六烷基三甲基溴化铵 (CTAB) 添加量等7 个因素对Gpn12 全细胞催化合成MK-3 的影响，发现催化温度、甲萘醌添加量、催化时间影响显著，对3 个显著因素进行响应面优化得出催化条件为：催化温度31.56 ℃，甲萘醌添加量295.54 mg/L，催化时间15.87 h，优化后的摇瓶MK-3 产量达到98.47 mg/L，与响应面预测结果一致，较优化前对照组提高了35%。在30 L 发酵罐进行生物催化实验，催化时间24 h，细胞催化剂浓度220 g (干重)/L，MK-3 产量达到189.67 mg/L。该方法为Gpn12 规模化生产MK-3 奠定了一定的基础。.

100 项与 Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性丙型肝炎	临床3期	-	Merck Sharp & Dohme LLC	2015-12-10
丙型肝炎	临床3期	丹麦	Merck GmbH	-
丙型肝炎	临床3期	法国	Merck GmbH	-
丙型肝炎	临床3期	法国	Merck GmbH	-
丙型肝炎	临床3期	丹麦	Merck GmbH	-

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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


NCT02661126 (MK-3682B-030 \| 3682B-030, CTgov)	临床1期	丙型肝炎	16	MK-3682B (Moderate RI Participants)	鹽鹽鏇繭構繭獵齋築壓(範窪齋範襯鏇範鹽夢遞) = 襯構襯壓製鏇蓋構網膚網襯醖顧夢蓋淵繭構鹹 (顧糧窪鹽憲醖齋鑰壓鏇, 餘築齋醖築積鬱艱鑰壓 ~ 鹹繭顧願蓋衊憲願膚積) 更多	-	2018-12-14
				MK-3682B (Healthy Participants)	鹽鹽鏇繭構繭獵齋築壓(範窪齋範襯鏇範鹽夢遞) = 壓獵襯窪廠鬱蓋積構餘網襯醖顧夢蓋淵繭構鹹 (顧糧窪鹽憲醖齋鑰壓鏇, 艱壓鬱餘積願糧衊膚衊 ~ 簾夢遞鏇網選顧觸獵淵) 更多
NCT02613403 (MK-3682-021 \| 3682-021, CTgov)	临床2期	慢性丙型肝炎	94	MK-3682B+Ribavirin ([Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV)	鬱遞夢餘鬱淵鏇繭積醖(艱願觸鹹襯衊淵鏇繭餘) = 鏇選簾獵鹽窪鏇餘餘蓋齋觸鹹觸獵蓋蓋糧齋廠 (網壓淵憲繭艱鏇壓獵壓, 衊積襯鑰蓋齋膚醖願淵 ~ 鹽齋廠糧繭夢製壓觸憲) 更多	-	2018-03-20
				MK-3682B ([Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B)	鬱遞夢餘鬱淵鏇繭積醖(艱願觸鹹襯衊淵鏇繭餘) = 築窪鏇範蓋鏇觸夢構鏇齋觸鹹觸獵蓋蓋糧齋廠 (網壓淵憲繭艱鏇壓獵壓, 鏇齋鏇廠廠鑰繭觸積膚 ~ 鹽鏇鏇鹽築窪鬱鏇構衊) 更多