IRAK4 (N Terminus)
- Known as:
- IRAK4 (N Terminus)
- Catalog number:
- Y213406
- Product Quantity:
- 200ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- IRAK4 ( Terminus)
Related genes to: IRAK4 (N Terminus)
- Gene:
- IRAK4 NIH gene
- Name:
- interleukin 1 receptor associated kinase 4
- Previous symbol:
- -
- Synonyms:
- NY-REN-64
- Chromosome:
- 12q12
- Locus Type:
- gene with protein product
- Date approved:
- 2002-09-27
- Date modifiied:
- 2019-04-23
Related products to: IRAK4 (N Terminus)
Related articles to: IRAK4 (N Terminus)
- Interleukin-1 receptor-associated kinase 2 (IRAK2) is essential for the Myddosome complex formation downstream of Toll-like receptors. We identify twelve patients with a homozygous loss-of-function copy number variant in IRAK2, designated IRAK2-∆ex2. Most patients present with recurrent infections, autoantibody production, and gastrointestinal ulceration. Two patients were clinically diagnosed with primary immunodeficiency, while the majority fulfill diagnostic criteria for autoimmune or autoinflammatory diseases. The IRAK2-∆ex2 protein fails to interact with IRAK4, leading to impaired activation of nuclear factor kappa B signaling via the Myddosome complex. An elevated type I interferon signature is observed in the patients, which is confirmed in bone marrow-derived macrophages from knock-in mice and knockout cell lines. Mechanistically, our data are consistent with engagement of a TRIF-dependent interferon pathway. Baricitinib attenuates the elevated interferon signature in patient-derived cells ex vivo and cell lines. Here, we show IRAK2 deficiency as a monogenic immune dysregulation disorder. - Source: PubMed
Publication date: 2026/05/21
Fei YudieLiu LinMa ShuangyueJin YingWang ShihaoZhang LiangYang JunLiu YiLu MeipingXue JingLi JingyiChen XiangWang JunYao YuhaoLiu ChenluZhang JiahuiHan XuFu JinjianKang ZhijuanWang YushaSun XiangweiZhang ChangmingHe TingyanLiu ZhihuiGuo LiChen ChengshunZhao HongmeiGao XingjianZhong HuaWen LihongYu XiaominLiu ZhihongZhou Qing - Proteolysis-targeting chimeras (PROTACs) represent a promising modality for targeted protein degradation, yet their structural complexity complicates systematic design and analysis. Bellerophon is a new computational tool that automatically decomposes PROTACs into their warhead, linker, and E3 ligase ligand directly from molecular structure. By enabling automated and standardized decomposition of degraders, the tool facilitates drug design at different levels: Bellerophon demonstrated versatility for moiety replacement (ARV-110), large-scale annotation (PROTAC-DB) and linker analysis (IRAK4 data set). The tool is freely available through a user-friendly web interface, with open-source code to encourage transparency and collaborative development in chemical biology and medicinal chemistry. - Source: PubMed
Publication date: 2026/04/10
Apprato GiuliaBertola MatteoLocatelli AmeliaCaron GiuliaMauri AndreaErmondi Giuseppe - Inflammation-driven tumor implantation, such as port-site metastasis (PSM) following laparoscopic gynecologic surgery and peritoneal seeding during post-surgical recurrence, represents an aggressive clinical problem that remains poorly understood and lacks targeted therapies. To address this, we developed a non-surgical Mesothelium-Inflammation/Injury-Metastasis (MIM) model and investigated the role of the IL-1β/IL1R1/MYD88/IRAK1/4 axis and NLRP3 in epithelial ovarian cancer (EOC) seeding at inflamed or injured sites. This model created by a needle injury recapitulates inflammation-driven peritoneal seeding and mimics PSM and inflammation associated dissemination in peritoneum during recurrence. Seeding was dependent on Il1r1 but not Nlrp3, despite its role in regulating IL-1β production, as Il1ra⁻/⁻ and Nlrp3⁻/⁻ mice phenocopied wild-type C57BL/6 mice. Given the limited antitumor efficacy of IL-1β-targeting agents such as Anakinra and Canakinumab, we focused on IRAK4 as a therapeutic target. IRAK4 knockdown significantly prolonged survival, reduced tumor cell adhesion, downregulated E-cadherin and Wnt4, and induced S-phase/mitotic arrest. This led to the development of UR241-2, a small-molecule IRAK4 inhibitor, which was validated through molecular simulations, hotspot analysis, nanoBRET, global kinome profiling, and NF-κβ reporter assays. UR241-2 inhibited NF-κβ nuclear translocation and blocked IL-1β-induced IRAK4 phosphorylation. UR241-2 exhibited favorable drug-like properties, including absence of CYP or hERG inhibition, and acceptable CaCo-2 permeability, plasma protein binding, microsomal stability, and pharmacokinetics. In vivo, UR241-2 reduced SKOV3 xenograft growth, suppressed mesothelial seeding, and increased MHC-II⁺ macrophages and activated neutrophils in syngeneic high-grade epithelial ovarian HGS3 tumors. RNA-seq revealed enrichment of neutrophil activation signatures and suppression of extracellular matrix (ECM) gene programs. Together, these findings establish a role for the IL-1β/IL1R1/IRAK4 axis in inflammation-driven PSM and peritoneal seeding and ECM regulation in EOC, and demonstrate that IRAK4 inhibition activates antitumor immune responses, providing a therapeutic strategy to block metastatic seeding and improve tumor control. - Source: PubMed
Publication date: 2026/05/05
Miller John PKim Kyu KwangSnyder Cameron WaKhazan NegarSingh Niloy ABoyer Megan ELamere ElizabethStrawderman MylaSharma SonaliLakony RonaldWhittum MichelleAnderson MarkKeenan RickPritchett ElizabethBaker CameronAshton JohnKhera Manoj KElliott Michael RAnnunziata Christina MBajaj JeevishaCalvi Laura MBecker Michael WRowswell-Turner RachaelMoore Richard GSingh Rakesh K - IRAK4 deficiency is a rare autosomal recessive inborn error of immunity caused by disruption of Toll-like receptor (TLR) signaling, and characterized by recurrent pyogenic bacterial infections and impaired inflammatory responses. Here, we reported an 11-year-old boy presenting with recurrent fever, rare severe brain calcification, and seizures. The persistently elevated C-reactive protein (CRP) levels suggested an underlying defect in innate immune signaling. Genetic analysis identified compound heterozygous variants in IRAK4, including a frameshift variant c.123dupA (p.Pro42Thrfs*4), and a missense variant c.543T>G (p.Asp181Glu). Functional analyses further demonstrated markedly reduced IRAK4 protein expression and impaired TLR-mediated signaling in the patient's peripheral blood and cells transfected with the variant sequences. Consistent with these findings, RNA-sequencing revealed dysregulation of innate immune pathways involved in cytokine and chemokine responses. Together, these results provide converging genetic, structural, and functional evidence supporting the pathogenicity of the identified IRAK4 variants. Our findings expand the variant and phenotype spectrum of IRAK4 deficiency, and underscore the essential role of IRAK4 in regulating innate immune signaling and host defense against bacterial infections. - Source: PubMed
Publication date: 2026/05/06
Zhang JiayaoFan ShiqiXie LinaTang KaichenSun MiaoChen QianZhang Xue - Interleukin-1 receptor-associated kinase 4 (IRAK4) is a promising therapeutic target for inflammatory diseases. However, inhibition of its kinase activity alone often results in incomplete blockade of inflammatory signaling and limited therapeutic efficacy. To address this limitation, we designed and synthesized a novel proteolysis-targeting chimera (PROTAC) aimed at degrading IRAK4. Among the synthesized compounds, GSI526 emerged as a potent degrader, demonstrating efficient IRAK4 degradation in THP-1 cells with a DC₅₀ of 40.17 nM. Mechanistic studies confirmed that GSI526 acts via the ubiquitin-proteasome system, effectively suppressing the IRAK4-mediated NF-κB and MAPK signaling pathways. Furthermore, GSI526 exhibited a favorable preliminary safety profile. Collectively, these findings identify GSI526 as a promising IRAK4-targeting degrader, offering an alternative therapeutic strategy and a candidate for further drug development. - Source: PubMed
Publication date: 2026/05/05
Yin BingjieGao ZhishuoMa YanLi ZhuoyueMa Mengjun