ArticleScientific reports2017
Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations.
Article in Scientific reports, 2017. 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, 60 citations in OpenAlex.
- Structure-based discovery of selective vaccinia-related kinase 1 inhibitors and fluorogenic active-site probes.The Journal of biological chemistry · 2026Article
- Polo-like kinase 1-inhibitor co-complex structures via the surface-entropy reduction approach and a DARPin-assisted approach.Acta crystallographica. Section D, Structural biology · 2025Article
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Design and Synthesis of Pyrazole-Based Macrocyclic Kinase Inhibitors Targeting BMPR2.ACS medicinal chemistry letters · 2023Article
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
- Decoding the Conformational Selective Mechanism of FGFR Isoforms: A Comparative Molecular Dynamics Simulation.Molecules (Basel, Switzerland) · 2023Article
- VRK1 Kinase Activity Modulating Histone H4K16 Acetylation Inhibited by SIRT2 and VRK-IN-1.International journal of molecular sciences · 2023Article
- Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell Carcinoma through DNA Damage.Canadian respiratory journal · 2023Article
- Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.Oncology research · 2023Article
- VRK1 Is a Synthetic-Lethal Target in VRK2-Deficient Glioblastoma.Cancer research · 2022Article
- Multivalent DNA and nucleosome acidic patch interactions specify VRK1 mitotic localization and activity.Nucleic acids research · 2022Article
- An overview of kinase downregulators and recent advances in discovery approaches.Signal transduction and targeted therapy · 2021Review
- Structural Basis for Targeting the Folded P-Loop Conformation of c-MET.ACS medicinal chemistry letters · 2021Article
- Interaction of obtusilactone B and related butanolide lactones with the barrier-to-autointegration factor 1 (BAF1). A computational study.Current research in pharmacology and drug discovery · 2021Article
- VRK1 Depletion Facilitates the Synthetic Lethality of Temozolomide and Olaparib in Glioblastoma Cells.Frontiers in cell and developmental biology · 2021Article
- Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation.Cancers · 2020Article
- Emerging roles of the αC-β4 loop in protein kinase structure, function, evolution, and disease.IUBMB life · 2020Review
- Development of Pyridine-based Inhibitors for the Human Vaccinia-related Kinases 1 and 2.ACS medicinal chemistry letters · 2019Article
- Crystal structure of human vaccinia-related kinase 1 in complex with AMP-PNP, a non-hydrolyzable ATP analog.Protein science : a publication of the Protein Society · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
Abstract
The human genome encodes two active Vaccinia-related protein kinases (VRK), VRK1 and VRK2. These proteins have been implicated in a number of cellular processes and linked to a variety of tumors. However, understanding the cellular role of VRKs and establishing their potential use as targets for therapeutic intervention has been limited by the lack of tool compounds that can specifically modulate the activity of these kinases in cells. Here we identified BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the development of chemical probes targeting the active VRKs. We solved co-crystal structures of both VRK1 and VRK2 bound to BI-D1870 and of VRK1 bound to two broad-spectrum inhibitors. These structures revealed that both VRKs can adopt a P-loop folded conformation, which is stabilized by different mechanisms on each protein. Based on these structures, we suggest modifications to the dihydropteridine scaffold that can be explored to produce potent and specific inhibitors towards VRK1 and VRK2.
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Registered trials
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