ArticlePloS one2020
3PO inhibits inflammatory NFκB and stress-activated kinase signaling in primary human endothelial cells independently of its target PFKFB3.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice.The Journal of biological chemistry · 2026Article
- Glucose Metabolic Enzyme PFKFB3 in Cardiopulmonary Vascular Health and Disease.Circulation research · 2026Review
- Metabolic Reprogramming and Cell Interaction in Atherosclerosis: From Molecular Mechanisms to Therapeutic Strategies.Journal of cardiovascular development and disease · 2025Review
- Targeting Lactic Acid Modification in Ischemic Heart Diseases: Novel Therapeutics and Mechanism.Journal of cardiovascular translational research · 2025Review
- The small molecule inhibitor 3PO is a modulator of neutrophil metabolism, ROS production, and NET release.Clinical and experimental immunology · 2025Article
- Metabolism in the tumor microenvironment: implications for pathogenesis and therapeutics.Frontiers in immunology · 2025Review
- Metabolic Regulation of Endothelial Cells: A New Era for Treating Wet Age-Related Macular Degeneration.International journal of molecular sciences · 2024Review
- The Impact of Glycolysis and Its Inhibitors on the Immune Response to Inflammation and Autoimmunity.Molecules (Basel, Switzerland) · 2024Review
- PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.Cell & bioscience · 2024Review
- Gene-dosage effect of Pfkfb3 on monocyte/macrophage biology in atherosclerosis.British journal of pharmacology · 2022Article
- Inflammatory activation of endothelial cells increases glycolysis and oxygen consumption despite inhibiting cell proliferation.FEBS open bio · 2021Article
- PFKFB3: A Potential Key to Ocular Angiogenesis.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of the key glycolytic activator 6-phosphofructokinase 2/fructose-2,6-bisphosphatase-3 (PFKFB3) by 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) strongly attenuates pathological angiogenesis in cancer and inflammation. In addition to modulating endothelial proliferation and migration, 3PO also dampens proinflammatory activation of endothelial cells and experimental inflammation in vivo, suggesting a potential for 3PO in the treatment of chronic inflammation. The aim of our study was to explore if the anti-inflammatory action of 3PO in human endothelial cells was mediated by inhibition of PFKFB3 and glycolysis and assess if other means of PFKFB3 inhibition reduced inflammatory activation in a similar manner. We found that 3PO caused a rapid and transient reduction in IL-1β- and TNF-induced phosphorylation of both IKKα/β and JNK, thus inhibiting signaling through the NFκB and the stress-activated kinase pathways. However, in contrast to 3PO-treatment, neither shRNA-mediated silencing of PFKFB3 nor treatment with the alternative PFKFB3 inhibitor 7,8-dihydroxy-3-(4-hydroxy-phenyl)-chromen-4-one (YN1) prevented cytokine-induced NFκB signaling and upregulation of the adhesion molecules VCAM-1 and E-selectin, implying off target effects of 3PO. Collectively, our results suggest that the anti-inflammatory action of 3PO in human endothelial cells is not limited to inhibition of PFKFB3 and cellular glycolysis.
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