ArticleScientific reports2018
Genetic and pharmacological validation of TAK1 inhibition in macrophages as a therapeutic strategy to effectively inhibit TNF secretion.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Blockade of Tumor TAK1 Induces DNA Damage and Immunogenic cGAS-STING Pathway Activation in Pancreatic Cancer.Gastroenterology · 2026Article
- Mapping the ATP-Binding Pockets of FLT3 and TAK1: A Structural Basis for Dual Inhibition by FLT3-Targeted Therapies.ACS chemical biology · 2026Article
- IL-4Rα signalling influences behavioural and immune responses in Trypanosoma brucei-infected mice: Evidence for iloprost as a neuroprotective agent.IBRO neuroscience reports · 2025Article
- TAK1 inhibition leads to RIPK1-dependent apoptosis in immune-activated cancers.Cell death & disease · 2024Article
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models.Journal of pain research · 2024Article
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.The journal of pain · 2023Article
- Delineation of the distinct inflammatory signaling roles of TAK1 and JAK1/3 in the CIA model of rheumatoid arthritis.Pharmacology research & perspectives · 2023Article
- Pharmacological inhibition of TAK1 prevents and induces regression of experimental organ fibrosis.JCI insight · 2023Article
- Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis.ACS chemical biology · 2022Article
- Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization.Theranostics · 2022Article
- Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway.International journal of molecular sciences · 2021Article
- NF-κB and Pancreatic Cancer; Chapter and Verse.Cancers · 2021Review
- Promise of the NLRP3 Inflammasome Inhibitors in In Vivo Disease Models.Molecules (Basel, Switzerland) · 2021Review
- Discovery of 2,4-1ACS medicinal chemistry letters · 2021Article
- Screening of Microbial Natural Products and Biological Evaluation of Trichomicin as Potential Anti-Cytokine Storm Agents.Frontiers in pharmacology · 2021Article
- Essential role of the linear ubiquitin chain assembly complex and TAK1 kinase in A20 mutant Hodgkin lymphoma.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases.Open biology · 2020Review
- TAK1 regulates the tumor microenvironment through inflammatory, angiogenetic and apoptotic signaling cascades.Oncotarget · 2020Article
- A highly selective inhibitor of interleukin-1 receptor-associated kinases 1/4 (IRAK-1/4) delineates the distinct signaling roles of IRAK-1/4 and the TAK1 kinase.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Immune challenge of invading macrophages at sites of infection is associated with release of TNF, which triggers a local cytokine storm as part of the normal inflammatory response. Whereas this response maybe beneficial in fighting off infections, similar responses triggered in autoimmune diseases contribute significantly to the underlying damaging pathology associated with these diseases. Here we show that Takinib, a highly discriminatory inhibitor of transforming growth factor Beta- activated kinase 1 (TAK1), selectively and potently reduces TNF production in pro-inflammatory THP-1 macrophages. A complete survey of 110 cytokines, showed robust loss of proinflammatory cytokine responsiveness to lipopolysaccharide (LPS) and interferon gamma (IFNγ) challenge in response to Takinib. The mechanisms of action of Takinib was recapitulated in TAK1 KO macrophages. TAK1 KO cells showed significant loss of TNF production as well as release of IL-6 in response to LPS challenge. Furthermore, Takinib blocked the ability of exogenously added LPS to promote phosphorylation of, c-Jun, p38 protein kinases as well as downstream transcription factors regulated by nuclear factor κ-light-chain-enhancer of activated B cells (NFκB). In a mouse LPS challenge model, Takinib significantly reduced TNF serum levels. Our findings demonstrate that Takinib has utility in the treatment inflammatory disease by locally suppressing TNF production from invading macrophages.
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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.