ArticleEBioMedicine2019
Targeting allosteric site of AKT by 5,7-dimethoxy-1,4-phenanthrenequinone suppresses neutrophilic inflammation.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
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- Identification of Fatty Acid Metabolism Disorder-Related Gene Signature in Septic Cardiomyopathy.Journal of inflammation research · 2025Article
- Discovery of 1,3-disubstituted prop-2-en-1-one derivatives as inhibitors of neutrophilic inflammation via modulation of MAPK and Akt pathways.Journal of enzyme inhibition and medicinal chemistry · 2024Article
- New phenanthrenequinones fromRSC advances · 2024Article
- Ribociclib leverages phosphodiesterase 4 inhibition in the treatment of neutrophilic inflammation and acute respiratory distress syndrome.Journal of advanced research · 2024Article
- Chemometric-guided chemical marker selection: A case study of the heat-clearing herbFrontiers in plant science · 2023Article
- Lonicerae Japonicae Flos Attenuates Neutrophilic Inflammation by Inhibiting Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Naphthoquinone as a New Chemical Scaffold for Leishmanicidal Inhibitors ofBiomedicines · 2022Article
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- Network Pharmacology and Experimental Validation to Explore the Mechanism of Qing-Jin-Hua-Tan-Decoction Against Acute Lung Injury.Frontiers in pharmacology · 2022Article
- Bletinib ameliorates neutrophilic inflammation and lung injury by inhibiting Src family kinase phosphorylation and activity.British journal of pharmacology · 2021Article
- Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70Scientific reports · 2021Article
- Focal Adhesion Kinase Inhibitor Inhibits the Oxidative Damage Induced by Central Venous Catheter via Abolishing Focal Adhesion Kinase-Protein Kinase B Pathway Activation.BioMed research international · 2021Article
- Novel Caryophyllane-Related Sesquiterpenoids with Anti-Inflammatory Activity fromMarine drugs · 2020Article
- Sponge-Derived 24-Homoscalaranes as Potent Anti-Inflammatory Agents.Marine drugs · 2020Article
- Transgelins: Cytoskeletal Associated Proteins Implicated in the Metastasis of Colorectal Cancer.Frontiers in cell and developmental biology · 2020Review
- A novel NOX2 inhibitor attenuates human neutrophil oxidative stress and ameliorates inflammatory arthritis in mice.Redox biology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcute lung injury (ALI) is a severe life-threatening inflammatory disease. Neutrophil activation is a major pathogenic factor in ALI. Protein kinase B (PKB)/AKT regulates diverse cellular responses, but the significance in neutrophilic inflammation and ALI remains unknown.
methodsHuman neutrophils and neutrophil-like differentiated HL-60 (dHL-60) cells were used to examine the anti-inflammatory effects of 5,7-dimethoxy-1,4-phenanthrenequinone (CLLV-1). The therapeutic potential of CLLV-1 was determined in a mouse model of lipopolysaccharide (LPS)-induced ALI.
findingsCLLV-1 inhibited respiratory burst, degranulation, adhesion, and chemotaxis in human neutrophils and dHL-60 cells. CLLV-1 inhibited the phosphorylation of AKT (Thr308 and Ser473), but not of ERK, JNK, or p38. Furthermore, CLLV-1 blocked AKT activity and covalently reacted with AKT Cys310 in vitro. The AKT
interpretationOur results identify CLLV-1 as a covalent allosteric AKT inhibitor by targeting AKT Cys310. CLLV-1 shows potent anti-inflammatory activity in human neutrophils and LPS-induced mouse ALI. Our findings provide a mechanistic framework for redox modification of AKT that may serve as a novel pharmacological target to alleviate neutrophilic inflammation.
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