ArticleThe Journal of biological chemistry2020
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.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Inflammation in atherosclerosis: Drivers, mechanisms and therapies.Acta pharmaceutica Sinica. B · 2026Review
- Mapping the ATP-Binding Pockets of FLT3 and TAK1: A Structural Basis for Dual Inhibition by FLT3-Targeted Therapies.ACS chemical biology · 2026Article
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- TLR7 and TLR9 have overlapping but distinct roles in systemic lupus erythematosus and Sjögren's disease.Frontiers in immunology · 2026Review
- Article
- Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritisFrontiers in pharmacology · 2024Article
- Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Alleviates Inflammatory Joint Pain in Osteoarthritis and Gouty Arthritis Preclinical Models.Journal of pain research · 2024Article
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- 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
- Key Genes of Immunity Associated with Pterygium and Primary Sjögren's Syndrome.International journal of molecular sciences · 2023Article
- Toll-like receptors 7 and 9 regulate the proliferation and differentiation of B cells in systemic lupus erythematosus.Frontiers in immunology · 2023Review
- Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway.Frontiers in immunology · 2023Article
- A Chemical Proteomic Map of Heme-Protein Interactions.Journal of the American Chemical Society · 2022Article
- Development and Efficacy of an Orally Bioavailable Selective TAK1 Inhibitor for the Treatment of Inflammatory Arthritis.ACS chemical biology · 2022Article
- Albiflorin Alleviates Ox-LDL-Induced Human Umbilical Vein Endothelial Cell Injury through IRAK1/TAK1 Pathway.BioMed research international · 2022Article
- Toll-like receptor signalling in B cells during systemic lupus erythematosus.Nature reviews. Rheumatology · 2021Review
- Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling.Mediators of inflammation · 2021Review
- Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Interleukin-1 receptor-associated kinase-1 (IRAK-1) and IRAK-4, as well as transforming growth factor β-activated kinase 1 (TAK1), are protein kinases essential for transducing inflammatory signals from interleukin receptors. IRAK family proteins and TAK1 have high sequence identity within the ATP-binding pocket, limiting the development of highly selective IRAK-1/4 or TAK1 inhibitors. Beyond kinase activity, IRAKs and TAK1 act as molecular scaffolds along with other signaling proteins, complicating the interpretation of experiments involving knockin or knockout approaches. In contrast, pharmacological manipulation offers the promise of targeting catalysis-mediated signaling without grossly disrupting the cellular architecture. Recently, we reported the discovery of takinib, a potent and highly selective TAK1 inhibitor that has only marginal activity against IRAK-4. On the basis of the TAK1-takinib complex structure and the structure of IRAK-1/4, here we defined critical contact sites of the takinib scaffold within the nucleotide-binding sites of each respective kinase. Kinase activity testing of takinib analogs against IRAK-4 identified a highly potent IRAK-4 inhibitor (HS-243). In a kinome-wide screen of 468 protein kinases, HS-243 had exquisite selectivity toward both IRAK-1 (IC
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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.