ArticleJournal of medicinal chemistry2018
Optimization of Isothiazolo[4,3- b]pyridine-Based Inhibitors of Cyclin G Associated Kinase (GAK) with Broad-Spectrum Antiviral Activity.
Article in Journal of medicinal chemistry, 2018. 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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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- AP2: an indispensable host factor in virus infection.Journal of virology · 2026Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- The Structure-Antiproliferative Activity Relationship of Pyridine Derivatives.International journal of molecular sciences · 2024Review
- Preparing for the next viral threat with broad-spectrum antivirals.The Journal of clinical investigation · 2023Review
- Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases.Viruses · 2023Review
- Seeking heterocyclic scaffolds as antivirals against dengue virus.European journal of medicinal chemistry · 2022Review
- The cargo adapter protein CLINT1 is phosphorylated by the Numb-associated kinase BIKE and mediates dengue virus infection.The Journal of biological chemistry · 2022Article
- Kinase Inhibitors as Underexplored Antiviral Agents.Journal of medicinal chemistry · 2022Review
- Article
- Optimization of 4-Anilinoquinolines as Dengue Virus Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- GAK and PRKCD are positive regulators of PRKN-independent mitophagy.Nature communications · 2021Article
- Antivirals against the Chikungunya Virus.Viruses · 2021Review
- Viral Interactions with Adaptor-Protein Complexes: A Ubiquitous Trait among Viral Species.International journal of molecular sciences · 2021Review
- Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.Journal of medicinal chemistry · 2021Article
- The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design.Drug design, development and therapy · 2021Review
- BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.Antiviral research · 2020Article
- Medicinal chemistry strategies toward host targeting antiviral agents.Medicinal research reviews · 2020Review
- Serine/Threonine Protein Kinase STK16.International journal of molecular sciences · 2019Review
- Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
There is an urgent need for strategies to combat dengue and other emerging viral infections. We reported that cyclin G-associated kinase (GAK), a cellular regulator of the clathrin-associated host adaptor proteins AP-1 and AP-2, regulates intracellular trafficking of multiple unrelated RNA viruses during early and late stages of the viral lifecycle. We also reported the discovery of potent, selective GAK inhibitors based on an isothiazolo[4,3- b]pyridine scaffold, albeit with moderate antiviral activity. Here, we describe our efforts leading to the discovery of novel isothiazolo[4,3- b]pyridines that maintain high GAK affinity and selectivity. These compounds demonstrate improved in vitro activity against dengue virus, including in human primary dendritic cells, and efficacy against the unrelated Ebola and chikungunya viruses. Moreover, inhibition of GAK activity was validated as an important mechanism of antiviral action of these compounds. These findings demonstrate the potential utility of a GAK-targeted broad-spectrum approach for combating currently untreatable emerging viral infections.
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Registered trials
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.