ArticleOncotarget2015
Mutation of cysteine 46 in IKK-beta increases inflammatory responses.
Article in Oncotarget, 2015. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Pharmacological mechanisms and potential clinical applications of Dihydromyricetin in neurological disorders.Frontiers in pharmacology · 2025Review
- IKKActa pharmaceutica Sinica. B · 2022Article
- Abnormal function of telomere protein TRF2 induces cell mutation and the effects of environmental tumor‑promoting factors (Review).Oncology reports · 2021Review
- Icaritin inhibits PD-L1 expression by Targeting Protein IκB Kinase α.European journal of immunology · 2021Article
- Quantum mechanics and 3D-QSAR studies on thienopyridine analogues: inhibitors of IKKβ.Heliyon · 2020Article
- Targeting IκappaB kinases for cancer therapy.Seminars in cancer biology · 2019Review
- Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma.Cell death & disease · 2017Article
- Succinamide derivatives of melampomagnolide B and their anti-cancer activities.Bioorganic & medicinal chemistry · 2017Article
- Isoliquiritigenin suppresses human T Lymphocyte activation via covalently binding cysteine 46 of IκB kinase.Oncotarget · 2017Article
- Dihydromyricetin Protects against Bone Loss in Ovariectomized Mice by Suppressing Osteoclast Activity.Frontiers in pharmacology · 2017Article
- The Versatile Effects of Dihydromyricetin in Health.Evidence-based complementary and alternative medicine : eCAM · 2017Review
- Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of IκB kinase β (IKK-β) and nuclear factor (NF)-κB signaling contributes to cancer pathogenesis and inflammatory disease; therefore, the IKK-β-NF-κB signaling pathway is a potential therapeutic target. Current drug design strategies focus on blocking NF-κB signaling by binding to specific cysteine residues on IKK-β. However, mutations in IKK-β have been found in patients who may eventually develop drug resistance. For these patients, a new generation of IKK-β inhibitors are required to provide novel treatment options. We demonstrate in vitro that cysteine-46 (Cys-46) is an essential residue for IKK-β kinase activity. We then validate the role of Cys-46 in the pathogenesis of inflammation using delayed-type hypersensitivity (DTH) and an IKK-β C46A transgenic mouse model. We show that a novel IKK-β inhibitor, dihydromyricetin (DMY), has anti-inflammatory effects on WT DTH mice but not IKK-β C46A transgenic mice. These findings reveal the role of Cys-46 in the promotion of inflammatory responses, and suggest that Cys-46 is a novel drug-binding site for the inhibition of IKK-β.
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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.