ArticleAntimicrobial agents and chemotherapy2014
In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- Trends in HIV-1 pretreatment drug resistance and HIV-1 variant dynamics among antiretroviral therapy-naive Ethiopians from 2003 to 2018: a pooled sequence analysis.Virology journal · 2023Pooled it
- Efficacy, Safety, and Tolerability of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate Fixed-Dose Combination Tablets in Adolescents Living With HIV: Results Through Week 96 from IMPAACT 2014.Journal of the Pediatric Infectious Diseases Society · 2023Trial
- A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV.Clinical drug investigation · 2021Trial
- Switching to Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) Maintains HIV-1 Virologic Suppression Through 48 Weeks: Results of the DRIVE-SHIFT Trial.Journal of acquired immune deficiency syndromes (1999) · 2019Trial
- Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- The Effect of Food on Doravirine Bioavailability: Results from Two Pharmacokinetic Studies in Healthy Subjects.Clinical drug investigation · 2017Trial
- Article
- Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Efficacy, safety, and anti-inflammatory properties of the switch to a doravirine-based regimen among antiretroviral-experienced elderly people living with HIV-1: the DORAGE cohort.Antimicrobial agents and chemotherapy · 2025Article
- An Amazing 30-Year Journey around the DABO Family: A Medicinal Chemistry Lesson on a Versatile Class of Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors.Journal of medicinal chemistry · 2025Review
- Mechanistic basis for a novel dual-function Gag-Pol dimerizer potentiating CARD8 inflammasome activation and clearance of HIV-infected cells.npj drug discovery · 2025Article
- Article
- K103N, V106M and Y188L Significantly Reduce HIV-1 Subtype C Phenotypic Susceptibility to Doravirine.Viruses · 2024Article
- Physicochemical Stability of Doravirine (PifeltroPharmaceutics · 2024Article
- The origin, dissemination, and molecular networks of HIV-1 CRF65_cpx strain in Hainan Island, China.BMC infectious diseases · 2024Article
- Multiscale topology in interactomic network: from transcriptome to antiaddiction drug repurposing.Briefings in bioinformatics · 2024Article
- Exploring novel HIV-1 reverse transcriptase inhibitors with drug-resistant mutants: A double mutant surprise.Protein science : a publication of the Protein Society · 2023Article
- Sequence-based drug design as a concept in computational drug design.Nature communications · 2023Article
- Article
Corrections and comments
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Authors and funding
19 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nonnucleoside reverse transcriptase inhibitors (NNRTIs) are a mainstay of therapy for treating human immunodeficiency type 1 virus (HIV-1)-infected patients. MK-1439 is a novel NNRTI with a 50% inhibitory concentration (IC50) of 12, 9.7, and 9.7 nM against the wild type (WT) and K103N and Y181C reverse transcriptase (RT) mutants, respectively, in a biochemical assay. Selectivity and cytotoxicity studies confirmed that MK-1439 is a highly specific NNRTI with minimum off-target activities. In the presence of 50% normal human serum (NHS), MK-1439 showed excellent potency in suppressing the replication of WT virus, with a 95% effective concentration (EC95) of 20 nM, as well as K103N, Y181C, and K103N/Y181C mutant viruses with EC95 of 43, 27, and 55 nM, respectively. MK-1439 exhibited similar antiviral activities against 10 different HIV-1 subtype viruses (a total of 93 viruses). In addition, the susceptibility of a broader array of clinical NNRTI-associated mutant viruses (a total of 96 viruses) to MK-1439 and other benchmark NNRTIs was investigated. The results showed that the mutant profile of MK-1439 was superior overall to that of efavirenz (EFV) and comparable to that of etravirine (ETR) and rilpivirine (RPV). Furthermore, E138K, Y181C, and K101E mutant viruses that are associated with ETR and RPV were susceptible to MK-1439 with a fold change (FC) of <3. A two-drug in vitro combination study indicated that MK-1439 acts nonantagonistically in the antiviral activity with each of 18 FDA-licensed drugs for HIV infection. Taken together, these in vitro data suggest that MK-1439 possesses the desired properties for further development as a new antiviral agent.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.