ArticleCell chemical biology2021
Exploiting polypharmacology to dissect host kinases and kinase inhibitors that modulate endothelial barrier integrity.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Host kinase regulation of Plasmodium vivax dormant and replicating liver stages.PLoS neglected tropical diseases · 2026Article
- Systems-level characterization of EGFR kinase inhibitors reveals heterogeneous effects on Mtb-macrophage interactions.bioRxiv : the preprint server for biology · 2025Article
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Chemoproteomic Profiling ofJournal of medicinal chemistry · 2025Article
- Using machine learning to dissect host kinases required for Leishmania internalization and development.Molecular and biochemical parasitology · 2024Article
- Systems-level reconstruction of kinase phosphosignaling networks regulating endothelial barrier integrity using temporal data.NPJ systems biology and applications · 2024Article
- Systems-level reconstruction of kinase phosphosignaling networks regulating endothelial barrier integrity using temporal data.bioRxiv : the preprint server for biology · 2024Article
- Using machine learning to dissect host kinases required forbioRxiv : the preprint server for biology · 2024Article
- Off-targets of BRAF inhibitors disrupt endothelial signaling and vascular barrier function.Life science alliance · 2024Article
- Interrogating endothelial barrier regulation by temporally resolved kinase network generation.Life science alliance · 2024Article
- Synthesis of Novel Nilotinib Analogues and Biological Evaluation of Their Antiplatelet Activity and Functionality towards Cancer Cell Proliferation In Vitro.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes.Frontiers in cellular and infection microbiology · 2024Article
- LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.Clinical and translational medicine · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Enterovirus A71 utilizes host cell lipid β-oxidation to promote its replication.Frontiers in microbiology · 2022Article
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Authors and funding
7 authors.
Funding
Abstract
Kinase inhibitors are promising drugs to stabilize the endothelial barrier following inflammatory damage. However, our limited knowledge of how kinase signaling activates barrier-restorative pathways and the complexity of multi-target drugs have hindered drug discovery and repurposing efforts. Here, we apply a kinase regression approach that exploits drug polypharmacology to investigate endothelial barrier regulation. A screen of 28 kinase inhibitors identified multiple inhibitors that promote endothelial barrier integrity and revealed divergent barrier phenotypes for BCR-ABL drugs. Target deconvolution predicted 50 barrier-regulating kinases from diverse kinase families. Using gene knockdowns, we identified kinases with a role in endothelial barrier regulation and dissected different mechanisms of action of barrier-protective kinase inhibitors. These results demonstrate the importance of polypharmacology in the endothelial barrier phenotype of kinase inhibitors and provide promising new leads for barrier-strengthening therapies.
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