Delving into the Latest Updates on Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Grazoprevir/MK-3682/MK-8408, Grazoprevir/MK-3682/ruzasvir, Grazoprevir/ruzasvir/MK-3682

+ [8]

Target

NS3/NS4A x NS5A x NS5B polymerase

Mechanism

NS3/NS4A inhibitors(Hepatitis C virus serine protease, NS3/NS4A inhibitors), NS5A inhibitors(Nonstructural protein 5A inhibitors), NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Hepatitis CHepatitis C, Chronic

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck Sharp & Dohme LLC

Merck Sharp & Dohme Corp.Merck GmbH

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H29ClN3O9P

InChIKeySFPFZQKYPOWCSI-KHFYHRBSSA-N

CAS Registry1496551-77-9

View All Structures (3)

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.

Start Date19 Jan 2016

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT02613403

/ TerminatedPhase 2

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.

Start Date10 Dec 2015

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT02332720

/ CompletedPhase 2

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).

Start Date28 Jan 2015

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir

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100 Translational Medicine associated with Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir

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100 Patents (Medical) associated with Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir

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21

Literatures (Medical) associated with Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir

01 Nov 2024·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

Author: 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.

30 Nov 2018·ACS OmegaQ3 · CHEMISTRY

Synthesis and Characterization of Partially and Fully Saturated Menaquinone Derivatives

Q3 · CHEMISTRY

ArticleOA

Author: 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).

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

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

Article

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

The effect of methanol addition on the heterologous expression of isoprenyl transferase NovQ was studied in Pichia pastoris Gpn12, with menadione and isopentenol as precursors to catalyze vitamin K2 (MK-3) synthesis. The expression of NovQ increased by 36% when 2% methanol was added every 24 h. The influence of initial pH, temperature, methanol addition, precursors (menadione, isopentenol) addition, catalytic time and cetyltrimethyl-ammonium bromide (CTAB) addition were explored in the P. pastoris whole-cell catalytic synthesis process of MK-3 in shaking flask. Three significant factors were then studied by response surface method. The optimal catalytic conditions obtained were as follows: catalytic temperature 31.56 ℃, menadione 295.54 mg/L, catalytic time 15.87 h. Consistent with the response surface prediction results, the optimized yield of MK-3 reached 98.47 mg/L in shaking flask, 35% higher than that of the control group. On this basis, the production in a 30-L fermenter reached 189.67 mg/L when the cell catalyst of 220 g/L (dry weight) was used to catalyze the synthesis for 24 h. This method laid the foundation for the large-scale production of MK-3 by P. pastoris Gpn12.

100 Deals associated with Grazoprevir Hydrate/Ruzasvir/Uprifosbuvir

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C, Chronic	Phase 3	-	Merck Sharp & Dohme LLC	10 Dec 2015
Hepatitis C	Phase 3	DK	Merck GmbH	-
Hepatitis C	Phase 3	FR	Merck GmbH	-
Hepatitis C	Phase 3	FR	Merck GmbH	-
Hepatitis C	Phase 3	DK	Merck GmbH	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02661126 (MK-3682B-030 \| 3682B-030, CTgov)	Phase 1	Hepatitis C	16	MK-3682B (Moderate RI Participants)	hmnqqddvyl(nxmukhhamz) = bfsdeeakzw faczrvlyve (jpfwnqhkmt, afcizfqyex - tekmzpxjiy) View more	-	14 Dec 2018
				MK-3682B (Healthy Participants)	hmnqqddvyl(nxmukhhamz) = imeqsniorb faczrvlyve (jpfwnqhkmt, tvalgovthp - rfpfvchlzf) View more
NCT02613403 (MK-3682-021 \| 3682-021, CTgov)	Phase 2	Hepatitis C, Chronic	94	MK-3682B+Ribavirin ([Part A, Arm 1] Prior SOF/LDV Failure: MK-3682B + RBV)	qkxpyvwxur(jkcfcluepx) = ebbkhwhxot ytvtfskgao (adpkbuxame, jqxxexqlqg - cyxwtnchqa) View more	-	20 Mar 2018
				MK-3682B ([Part A, Arm 2] Prior SOF/LDV Failure: MK-3682B)	qkxpyvwxur(jkcfcluepx) = zwzjfgpdbp ytvtfskgao (adpkbuxame, mjugufnxto - kjdddaidjd) View more