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

权益机构-

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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23

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

2025-03-24·International Journal of Systematic and Evolutionary Microbiology

Marivivens marinum sp. nov., isolated from tidal flat, Gochang, South Korea

Article

作者: Lee, Sang-Seob ; Kang, Min-Seok ; Srinivasan, Sathiyaraj ; Yu, Jae-yon ; Kim, Hyung-Seop

A Gram-negative, rod-shaped, non-motile, aerobic bacterium, designated MK-3T, was isolated from shallow seawater in Gochang, Republic of Korea. Growth of strain MK-3T occurred at 15–40 °C (30 °C), pH 6.0–7.0 (pH 7.0) and in the presence of 2–3 % NaCl (2%). Phylogenetic analysis based on the 16S rRNA gene sequence placed strain MK-3T within the family Roseobacteraceae. It exhibited sequence similarities of 95.7% with Salipiger marinus CK-I3-6T, Salipiger aestuarii DSM 22011T and Salipiger pentaromativorans P9T; 95.4% with Ruegeria alba 1NDH52CT, Salipiger manganoxidans VSW210T and Salipiger thiooxidans DSM 10146T; 95.3% with Marivivens donghaensis AM-4T and Histidinibacterium lentulum B17T; and 95.2% with Marivivens geojensis FJ12T. Phylogenetic and phylogenomic analyses consistently demonstrated that strain MK-3T formed a distinct lineage within the genus Marivivens, clustering with its closest relatives. The major fatty acids were C18 : 1 ω7c/C18 : 1 ω6c, C18 : 1 ω7c 11-methyl and C16 : 0. The genome length of strain MK-3T was 3.3 Mbp, and the DNA G+C content was 62.8 mol%. The strain contained Q-10 as the major ubiquinone. The polar lipids consisted of three phosphatidylinositol mannosides and a diphosphatidylglycerol. Based on its phenotypic, chemotaxonomic, phylogenetic and genomic characteristics, strain MK-3T represents a novel species in the genus Marivivens, for which the name Marivivens marinum sp. nov. is proposed. The type strain is MK-3T (=KEMB 21417T=KCTC 8294T=JCM 36630T).

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

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).

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)	網鏇衊窪顧築淵網簾鏇(艱鬱鹹鹽齋選網蓋襯襯) = 鑰範憲願築鹽餘蓋糧簾醖壓鹽鹹選衊繭網鑰壓 (顧廠鏇鹹願壓觸鬱醖鑰, 蓋糧鹽鏇窪願衊蓋餘鑰 ~ 艱鏇蓋繭淵憲顧窪糧製) 更多	-	2018-12-14
				MK-3682B (Healthy Participants)	網鏇衊窪顧築淵網簾鏇(艱鬱鹹鹽齋選網蓋襯襯) = 築築壓淵遞製鏇繭襯膚醖壓鹽鹹選衊繭網鑰壓 (顧廠鏇鹹願壓觸鬱醖鑰, 鏇遞顧積齋鏇遞膚艱鏇 ~ 鹽衊蓋積膚鏇鏇餘遞憲) 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)	繭鹽觸餘蓋艱窪醖淵憲(衊願膚鑰觸窪襯範夢簾) = 鑰積衊鑰淵憲窪範製鑰鹹廠觸蓋積齋觸餘窪遞 (構遞築鑰網構憲鹹衊顧, 壓淵構願膚淵衊積襯廠 ~ 襯憲淵餘艱壓夢繭觸醖) 更多	-	2018-03-20
				MK-3682B ([Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B)	繭鹽觸餘蓋艱窪醖淵憲(衊願膚鑰觸窪襯範夢簾) = 壓遞糧鑰衊網鹽網糧膚鹹廠觸蓋積齋觸餘窪遞 (構遞築鑰網構憲鹹衊顧, 憲窪範鏇積顧艱積積構 ~ 憲膚窪醖觸夢壓醖襯窪) 更多