{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(5)"],"submitter":["Tichenor MS"],"pubmed_abstract":["Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in the activation of B cells, macrophages, and osteoclasts. Given the key role of these cell types in the pathology of autoimmune disorders, BTK inhibitors have the potential to improve treatment outcomes in multiple diseases. Herein, we report the discovery and characterization of a novel potent and selective covalent 4-oxo-4,5-dihydro-3<i>H</i>-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide BTK inhibitor chemotype. Compound <b>27</b> irreversibly inhibits BTK by targeting a noncatalytic cysteine residue (Cys481) for covalent bond formation. Compound <b>27</b> is characterized by selectivity for BTK, potent <i>in vivo</i> BTK occupancy that is sustained after it is cleared from systemic circulation"],"journal":["ACS medicinal chemistry letters"],"pagination":["782-790"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8155241"],"repository":["biostudies-literature"],"pubmed_title":["Discovery of a Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase with Oral Anti-Inflammatory Activity."],"pmcid":["PMC8155241"],"pubmed_authors":["Wu J","Chang L","Edwards JP","Venable JD","Rao NL","Pooley Deckhut C","Leonard KA","Bacani GM","Seierstad M","Wiener JJM","Kreutter KD","Huber M","Lebsack AD","Murrey HE","Tichenor MS","Ahn K","Rex E","Coe KJ","Wang W","Bembenek SD","Barbay JK","Wei J"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of a Potent and Selective Covalent Inhibitor of Bruton's Tyrosine Kinase with Oral Anti-Inflammatory Activity.","description":"Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in the activation of B cells, macrophages, and osteoclasts. Given the key role of these cell types in the pathology of autoimmune disorders, BTK inhibitors have the potential to improve treatment outcomes in multiple diseases. Herein, we report the discovery and characterization of a novel potent and selective covalent 4-oxo-4,5-dihydro-3<i>H</i>-1-thia-3,5,8-triazaacenaphthylene-2-carboxamide BTK inhibitor chemotype. Compound <b>27</b> irreversibly inhibits BTK by targeting a noncatalytic cysteine residue (Cys481) for covalent bond formation. Compound <b>27</b> is characterized by selectivity for BTK, potent <i>in vivo</i> BTK occupancy that is sustained after it is cleared from systemic circulation","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2025-04-04T20:16:04.904Z","creation":"2025-04-04T20:16:04.904Z"},"accession":"S-EPMC8155241","cross_references":{"pubmed":["34055226"],"doi":["10.1021/acsmedchemlett.1c00044"]}}