ArticleACS medicinal chemistry letters2020
Discovery of a Selective, Covalent IRAK1 Inhibitor with Antiproliferative Activity in MYD88 Mutated B-Cell Lymphoma.
Article in ACS medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
- Discovery of JH-XIII-05-01, a First-in-Class Dual IRAK1/IRAK4 Degrader for MYD88 Mutant Lymphomas.ACS medicinal chemistry letters · 2026Article
- Phosphoregulation of interleukin-1 receptor-associated kinase 1 in inflammatory signaling.Frontiers in immunology · 2026Review
- Accelerated hit identification with target evaluation, deep learning and automated labs: prospective validation in IRAK1.Journal of cheminformatics · 2024Article
- Review
- Selective targeting of IRAK1 attenuates low molecular weight hyaluronic acid-induced stemness and non-canonical STAT3 activation in epithelial ovarian cancer.Cell death & disease · 2024Article
- Recent Advances in IRAK1: Pharmacological and Therapeutic Aspects.Molecules (Basel, Switzerland) · 2024Review
- Review
- Modulation of IRAK enzymes as a therapeutic strategy against SARS-CoV-2 induced cytokine storm.Clinical and experimental medicine · 2023Review
- IRAK1 inhibition blocks the HIV-1 RNA mediated pro-inflammatory cytokine response from microglia.The Journal of general virology · 2023Article
- Nonhematopoietic IRAK1 drives arthritis via neutrophil chemoattractants.JCI insight · 2022Article
- Interleukin-1 receptor associated kinase 1 (IRAK1) is epigenetically activated in luminal epithelial cells in prostate cancer.Frontiers in oncology · 2022Article
- IRAK1 and IRAK4 as emerging therapeutic targets in hematologic malignancies.Current opinion in hematology · 2022Review
- 1,4-Naphthoquinone Is a Potent Inhibitor of IRAK1 Kinases and the Production of Inflammatory Cytokines in THP-1 Differentiated Macrophages.ACS omega · 2021Article
- Multidimensional Mutational Profiling of the Indian HNSCC Sub-Population Provides IRAK1, a Novel Driver Gene and Potential Druggable Target.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Interleukin 1 (IL-1) receptor-associated kinases (IRAKs) are serine/threonine kinases that play critical roles in initiating the innate immune response against foreign pathogens. Additionally, dysregulation of IRAK1 signaling plays a role in neoplastic disorders. For example, IRAK1 was shown to be important for survival and proliferation in many B-cell lymphomas, including Waldenström's macroglobulinemia (WM) and ABC subtype Diffused Large B-cell Lymphoma (DLBCL) cells. Here, we report the discovery of a highly potent and selective covalent inhibitor of IRAK1, JH-X-119-01. Intact protein MS labeling studies confirmed that JH-X-119-01 irreversibly labels IRAK1 at C302. This compound exhibited cytotoxic activity at single digit micromolar concentrations in a panel of WM, DLBCL, and lymphoma cell lines expressing MYD88. Cotreatment of JH-X-119-01 with the BTK inhibitor ibrutinib resulted in synergistic killing effects in these systems. Taken together, JH-X-119-01 represents a highly selective probe of IRAK1 for further development.
Identifiers
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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.