PCI-31523

PCI-31523 is a selective and irreversible small molecule inhibitor of Bruton's tyrosine kinase (BTK). It functions by forming a covalent bond with the Cys-481 residue in the BTK active site, leading to potent inhibition (IC50 < 1 nM) and high selectivity over related kinases like Lck. By preventing BTK-mediated phosphorylation of phospholipase C-gamma (PLCg), the compound effectively disrupts B cell receptor (BCR) signaling pathways. Preclinical studies demonstrated its cytotoxic potential against B cell malignancies, such as diffuse large B cell lymphoma (DLBCL) and follicular lymphoma, as well as anti-inflammatory activity in animal models of rheumatoid arthritis. PCI-31523 is primarily recognized as a research tool and a structural precursor in the development of the first-in-class BTK inhibitor ibrutinib (PCI-32765).