ArticleAntimicrobial agents and chemotherapy2009
Antiviral activity of MK-4965, a novel nonnucleoside reverse transcriptase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed.
- Review
- Identification of 3-((1-(Benzyl(2-hydroxy-2-phenylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrazine-2-carboxylic Acid as a Potential Inhibitor of Non-Nucleosidase Reverse Transcriptase Inhibitors through InSilico Ligand- and Structure-Based Approaches.Molecules (Basel, Switzerland) · 2021Article
- Effect of Plasma Protein Binding on the Anti-Hepatitis B Virus Activity and Pharmacokinetic Properties of NVR 3-778.Antimicrobial agents and chemotherapy · 2018Article
- From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor-Associated Mutants at Clinically Relevant Concentrations.Antimicrobial agents and chemotherapy · 2016Article
- Derivatives of mesoxalic acid block translocation of HIV-1 reverse transcriptase.The Journal of biological chemistry · 2015Article
- In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication.Antimicrobial agents and chemotherapy · 2015Article
- In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2014Article
- In vitro and in vivo activities of AIC292, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2013Article
- Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability.Journal of the International AIDS Society · 2013Review
- Antiviral activity and in vitro mutation development pathways of MK-6186, a novel nonnucleoside reverse transcriptase inhibitor.Antimicrobial agents and chemotherapy · 2012Article
- F18, a novel small-molecule nonnucleoside reverse transcriptase inhibitor, inhibits HIV-1 replication using distinct binding motifs as demonstrated by resistance selection and docking analysis.Antimicrobial agents and chemotherapy · 2012Article
- Inhibitory activity of 9-phenylcyclohepta[d]pyrimidinedione derivatives against different strains of HIV-1 as non-nucleoside reverse transcriptase inhibitors.Virology journal · 2011Article
- Small-molecule inhibition of human immunodeficiency virus type 1 infection by virus capsid destabilization.Journal of virology · 2011Article
- Design, synthesis, and evaluation of diarylpyridines and diarylanilines as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.Journal of medicinal chemistry · 2010Article
- Distinct mutation pathways of non-subtype B HIV-1 during in vitro resistance selection with nonnucleoside reverse transcriptase inhibitors.Antimicrobial agents and chemotherapy · 2010Article
- Development of hexadecyloxypropyl tenofovir (CMX157) for treatment of infection caused by wild-type and nucleoside/nucleotide-resistant HIV.Antimicrobial agents and chemotherapy · 2010Article
- MK-7009, a potent and selective inhibitor of hepatitis C virus NS3/4A protease.Antimicrobial agents and chemotherapy · 2010Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are the mainstays of therapy for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, the effectiveness of NNRTIs can be hampered by the development of resistance mutations which confer cross-resistance to drugs in the same class. Extensive efforts have been made to identify new NNRTIs that can suppress the replication of the prevalent NNRTI-resistant viruses. MK-4965 is a novel NNRTI that possesses both diaryl ether and indazole moieties. The compound displays potency at subnanomolar concentrations against wild-type (WT), K103N, and Y181C reverse transcriptase (RT) in biochemical assays. MK-4965 is also highly potent against the WT virus and two most prevalent NNRTI-resistant viruses (viruses that harbor the K103N or the Y181C mutation), against which it had 95% effective concentrations (EC(95)s) of <30 nM in the presence of 10% fetal bovine serum. The antiviral EC(95) of MK-4965 was reduced approximately four- to sixfold when it was tested in 50% human serum. Moreover, MK-4965 was evaluated with a panel of 15 viruses with NNRTI resistance-associated mutations and showed a superior mutant profile to that of efavirenz but not to that of etravirine. MK-4965 was similarly effective against various HIV-1 subtypes and viruses containing nucleoside reverse transcriptase inhibitor or protease inhibitor resistance-conferring mutations. A two-drug combination study showed that the antiviral activity of MK-4965 was nonantagonistic with each of the 18 FDA-licensed drugs tested vice versa in the present study. Taken together, these in vitro data show that MK-4965 possesses the desired properties for further development as a new NNRTI for the treatment of HIV-1 infection.
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