This is a 2 part study of the safety, pharmacokinetics and pharmacodynamics of MK-6325 in HCV-infected participants. Part I of the study will be for Genotype (GT) 1 HCV-infected participants who will be randomized to receive either MK-6325 or placebo. If the drug is shown to be safe and efficacious in Part I, Part II will enroll GT 3 HCV-infected participants who will be randomized to receive either MK-6325 or placebo.

Start Date01 May 2011

Sponsor / Collaborator

Merck Sharp & Dohme Corp.

100 Clinical Results associated with MK-6325

100 Translational Medicine associated with MK-6325

100 Patents (Medical) associated with MK-6325

Literatures (Medical) associated with MK-6325

01 Jan 2019·Life sciencesQ3 · MEDICINE

A comparative study of the efficiency of HCV NS3/4A protease drugs against different HCV genotypes using in silico approaches

Q3 · MEDICINE

Article

Author: Elshemey, Wael M ; Ezat, Ahmed A

AIMS:

To investigate the efficacy of Direct Acting Antivirals (DAAs) in the treatment of different Hepatitis C Virus (HCV) genotypes.

MAIN METHODS:

Homology modeling is used to predict the 3D structures of different genotypes while molecular docking is employed to predict genotype - drug interactions (Binding Mode) and binding free energy (Docking Score).

KEY FINDINGS:

Simeprevir (TMC435) and to a lesser degree MK6325 are the best drugs among the studied drugs. The predicted affinity of drugs against genotype 1a is always better than other genotypes. P2-P4 macrocyclic drugs show better performance against genotypes 2, 3 and 5. Macrocyclic drugs are better than linear drugs.

SIGNIFICANCE:

HCV is one of the major health problems worldwide. Until the discovery of DAAs, HCV treatment faced many failures. DAAs target key functional machines of the virus life cycle and shut it down. NS3/4A protease is an important target and several drugs have been designed to inhibit its functions. There are several NS3/4A protease drugs approved by Food and Drug Administration (FDA). Unfortunately, the virus exhibits resistance against these drugs. This study is significant in elucidating that no one drug is able to treat different genotypes with the same efficiency. Therefore, treatment should be prescribed based on the HCV genotype.

08 Dec 2016·ACS medicinal chemistry lettersQ3 · MEDICINE

Design and Synthesis of P2–P4 Macrocycles Containing a Unique Spirocyclic Proline: A New Class of HCV NS3/4A Inhibitors

Q3 · MEDICINE

Article

Author: Chelliah, Mariappan ; Shah, Unmesh ; Xia, Yan ; Chackalamannil, Samuel ; Neelamkavil, Santhosh ; Howe, John ; Velázquez, Francisco ; Venkatraman, Srikanth ; Soriano, Aileen ; Clasby, Martin ; Davies, Ian W. ; Miller, Randy ; Guo, Zhuyan

A new class of hepatitis C NS3/4A inhibitors was identified by introducing a novel spirocyclic proline-P2 surrogate onto the P2-P4 macrocyclic core of MK-5172 (grazoprevir). The potency profile of new analogues showed excellent pan-genotypic activity for most compounds. The potency evaluation included the most difficult genotype 3a (EC₅₀ values ≤10 nM) and other key genotype 1b mutants. Molecular modeling was used to design new target compounds and rationalize our results. A synthetic approach based on the Julia-Kocienski olefination and macrolactamization to assemble the P2-P4 macrocyclic core containing the novel spirocyclic proline-P2 moiety is presented as well.

07 Mar 2016·Angewandte Chemie (International ed. in English)Q1 · CHEMISTRY

Olefin Metathesis at the Dawn of Implementation in Pharmaceutical and Specialty‐Chemicals Manufacturing

Q1 · CHEMISTRY

Review

Author: Carolyn S. Higman ; Deryn E. Fogg ; Justin A. M. Lummiss

Abstract:

The recent uptake of molecular metathesis catalysts in specialty‐chemicals and pharmaceutical manufacturing is reviewed.

100 Deals associated with MK-6325

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C, Chronic	Phase 1	-	Merck Sharp & Dohme Corp.	01 May 2011
Hepatitis C	Phase 1	Germany	Merck GmbH	-
Hepatitis C	Phase 1	Moldova	Merck GmbH	-

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