Delving into the Latest Updates on Uprifosbuvir with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Uprifosbuvir (USAN/INN)

+ [2]

Target

NS5B polymerase

Action

inhibitors

Mechanism

NS5B polymerase inhibitors(Hepatitis C virus NS5B RNA-dependent RNA polymerase inhibitors)

Therapeutic Areas

Infectious DiseasesDigestive System Disorders

Active Indication-

Inactive Indication

Chronic hepatitis C genotype 1Hepatitis C

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck GmbH

Merck Sharp & Dohme Corp.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC22H29ClN3O9P

InChIKeySFPFZQKYPOWCSI-KHFYHRBSSA-N

CAS Registry1496551-77-9

This is a nonrandomized, multi-site, open-label trial to evaluate a novel two-drug combination regimen (uprifosbuvir [MK-3682] 450 mg + ruzasvir [RZR; MK-8408] 180 mg once daily [q.d.] for 12 weeks) in male and female treatment-naïve (TN) or treatment-experienced (TE) participants with chronic hepatitis C virus (HCV) infection genotype (GT) GT1, GT2, GT3, GT4, GT5, or GT6 who have not previously received HCV direct-acting antiviral (DAA) therapy. Cirrhotic (C) and non-cirrhotic (NC) participants with and without human immunodeficiency virus (HIV) co-infection will be enrolled.

Start Date16 Nov 2016

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

NCT02759315

/ TerminatedPhase 2

A Phase II, Open-Label Clinical Trial to Study the Efficacy and Safety of the Combination Regimen of MK-3682 + MK-8408 in Subjects With Chronic HCV Genotype 1, 2, 3, 4, 5 or 6 Infection

This study is an open-label, multi-center trial to evaluate the novel 2-drug regimen of uprifosbuvir (MK-3682) 450 mg and ruzasvir (MK-8408) 60 mg in participants with chronic hepatitis C virus (HCV) genotype (GT)1, GT2, GT3, GT4, GT5, or GT6 infection. The impact of the study treatment regimen on the percentage of participants with undetectable HCV ribonucleic acid [RNA] 12 weeks after completing study treatment (SVR12) will be evaluated.

Start Date03 May 2016

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with Uprifosbuvir

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100 Translational Medicine associated with Uprifosbuvir

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100 Patents (Medical) associated with Uprifosbuvir

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44

Literatures (Medical) associated with Uprifosbuvir

22 Nov 2023·Journal of Biomolecular Structure and Dynamics

In silicostructural elucidation of Nipah virus L protein and targeting RNA-dependent RNA polymerase domain by nucleoside analogs

Article

Author: Sayed, El-Sayed T. A. ; Abduljalil, Jameel M. ; AlKhazindar, Maha M. ; Elfiky, Abdo A.

The large (L) protein of Mononegavirales is a multi-domain protein that performs transcription and genome replication. One of the important domains in L is the RNA-dependent RNA polymerase (RdRp), a promising target for antiviral drugs. In this work, we employed rigorous computational comparative modeling to predict the structure of L protein of Nipah virus (NiV). The RdRp domain was targeted by a panel of nucleotide analogs, previously reported to inhibit different viral RNA polymerases, using molecular docking. Best binder compounds were subjected to molecular dynamics simulation to validate their binding. Molecular mechanics/generalized-born surface area (MM/GBSA) calculations estimated the binding free energy. The predicted model of NiV L has an excellent quality as judged by physics- and knowledge-based validation tests. Galidesivir, AT-9010 and Norov-29 scored the top nucleotide analogs to bind to the RdRp. Their binding free energies obtained by MM/GBSA (-31.01 ± 3.9 to -38.37 ± 4.8 kcal/mol) ranked Norov-29 as the best potential inhibitor. Purine nucleotide analogs are expected to harbor the scaffold for an effective drug against NiV. Finally, this study is expected to provide a start point for medicinal chemistry and drug discovery campaigns toward identification of effective chemotherapeutic agent(s) against NiV.Communicated by Ramaswamy H. Sarma.

01 Aug 2023·Virology

Differential activity of nucleotide analogs against tick-borne encephalitis and yellow fever viruses in human cell lines

Article

Author: Bukh, Jens ; Galli, Andrea ; Binderup, Alekxander ; Fossat, Nicolas ; Fahnøe, Ulrik ; Scheel, Troels K H ; Mikkelsen, Lotte S ; Rivera-Rangel, Lizandro René ; Fernandez-Antunez, Carlota ; Ramirez, Santseharay

With no approved antiviral therapies, the continuous emergence and re-emergence of tick-borne encephalitis virus (TBEV) and yellow fever virus (YFV) is a rising concern. We performed head-to-head comparisons of the antiviral activity of available nucleos(t)ide analogs (nucs) using relevant human cell lines. Eight existing nucs inhibited TBEV and/or YFV with differential activity between cell lines and viruses. Remdesivir, uprifosbuvir and sofosbuvir were the most potent drugs against TBEV and YFV in liver cells, but they had reduced activity in neural cells, whereas galidesivir retained uniform activity across cell lines and viruses. Ribavirin, valopicitabine, molnupiravir and GS-6620 exhibited only moderate antiviral activity. We found antiviral activity for drugs previously reported as inactive, demonstrating the importance of using human cell lines and comparative experimental assays when screening the activity of nucs. The relatively high antiviral activity of remdesivir, sofosbuvir and uprifosbuvir against TBEV and YFV merits further investigation in clinical studies.

16 Sep 2022·Organic Process Research & Development

Manufacturing Process Development for Uprifosbuvir (MK-3682): A Green and Sustainable Process for Preparing Penultimate 2′-Deoxy-α-2′-Chloro-β-2′-Methyluridine

Author: Green, Meredith ; Calabria, Ralph ; Ye, Honglin ; Peng, Feng ; Zultanski, Susan L. ; Tong, Weidong ; Tan, Lushi ; Waldman, Jacob H. ; Moment, Aaron ; Liu, Guiquan ; Zhao, Ralph ; Chen, Wenyong ; Shevlin, Michael ; Zhou, George ; Limanto, John ; Ruck, Rebecca T. ; Zompa, Michael A. ; Dormer, Peter G. ; Hyde, Alan M. ; Song, Zhiguo Jake ; Klapars, Artis ; Nowak, Timothy ; Campeau, Louis-Charles ; Liu, Yizhou ; He, Cyndi Qixin ; Larsen, Mona Utne ; Maligres, Peter E.

A simple and efficient process to prepare Uprifosbuvir intermediate, 2′-deoxy-α-2′-chloro-β-2′-methyluridine, from bis-pivaloyl tertiary alc. is described.The key discoveries are a novel BSA-promoted anhydrouridine formation catalyzed by HCl as an additive and a milder safe Me₂SiCl₂-promoted chlorination of anhydrouridine.These discoveries collectively enabled the establishment of a robust process toward 2′-deoxy-α-2′-chloro-β-2′-methyluridine, which was demonstrated successfully at the plant scale.

100 Deals associated with Uprifosbuvir

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External Link

KEGG	Wiki	ATC	Drug Bank
D10996	Uprifosbuvir	-	DB15206

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 2	United Kingdom	Merck GmbH	-
Hepatitis C	Phase 2	Sweden	Merck GmbH	-
Hepatitis C	Phase 2	Belgium	Merck GmbH	-
Hepatitis C	Phase 2	United States	Merck GmbH	-
Hepatitis C	Phase 2	Belgium	Merck GmbH	-
Hepatitis C	Phase 2	United States	Merck GmbH	-
Hepatitis C	Phase 2	United Kingdom	Merck GmbH	-
Hepatitis C	Phase 2	Sweden	Merck GmbH	-
Hepatitis C	Phase 2	Lithuania	Merck GmbH	-
Hepatitis C	Phase 2	Lithuania	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


NCT02956629 (C-BREEZE 2 \| MK-3682-041 \| 3682-041, Pubmed \| J Viral Hepat) Manual	Phase 2	Hepatitis C, Chronic	282	Ruzasvir+uprifosbuvir	(uzczchkvei) = nvbkmfnhdt iqnwfllroa (ebxxcgysnw ) View more	Positive	01 Sep 2019
NCT02759315 (3682-035 \| MK-3682-035, Pubmed \| J Viral Hepat)	Phase 2	Hepatitis C	160	Ruzasvir 60 mg + Uprifosbuvir 450 mg	(kkehvhrdhn) = dpisweohcp oudxwcskxj (llvqymeeot )	-	01 Jun 2019
NCT02956629 (C-BREEZE 2 \| MK-3682-041 \| 3682-041, CTgov)	Phase 2	Hepatitis C, Chronic	282	Uprifosbuvir+Ribavirin+Ruzasvir (HCV GT1)	kcrmfbumth(swatfzighs) = fvmsroykxb xipcnmzhqr (mglbxdpfrb, blthqukyce - gkyonfwnxq) View more	-	26 Dec 2018
				Uprifosbuvir+Ribavirin+Ruzasvir (HCV GT2)	kcrmfbumth(swatfzighs) = ypzvlymrzi xipcnmzhqr (mglbxdpfrb, ptjhkibcyu - qsosdndsdv) View more
NCT02666352 (3682-029, CTgov)	Phase 1	Hepatitis C, Chronic	24	Uprifosbuvir+Ruzasvir (Moderate HI Participants)	wxfkfnevxc(dwlolglzpp) = xwhdncdxyx csagdxjipp (fefduwyjsl, lfgifxzhuh - sctrbjwcrr) View more	-	17 Sep 2018
				Uprifosbuvir+Ruzasvir (Severe HI Participants)	wxfkfnevxc(dwlolglzpp) = fojxxelobx csagdxjipp (fefduwyjsl, upnpqhxkzi - zxqmzxaesx) View more
NCT02759315 (3682-035 \| MK-3682-035, CTgov)	Phase 2	Chronic hepatitis C genotype 1	160	Uprifosbuvir 450 mg+Ruzasvir 60 mg (GT1: Uprifosbuvir 450 mg + Ruzasvir 60 mg)	kgtyoppbeq(yyoytdcwrq) = slrefkouql rlntmziufc (vctqkbxgwz, ylkermjnue - tbjdhbqsjc) View more	-	06 Aug 2018
				Uprifosbuvir 450 mg+Ruzasvir 60 mg (GT2: Uprifosbuvir 450 mg + Ruzasvir 60 mg)	kgtyoppbeq(yyoytdcwrq) = nesfvvpsvy rlntmziufc (vctqkbxgwz, wibrbxxwfn - yqlicmnchs) View more