BLU9931 is a highly selective covalent inhibitor targeting the BTK (Bruton's tyrosine kinase) enzyme, specifically designed to act on the C481S mutant form of BTK. This mutation commonly arises in patients with B-cell malignancies who have developed resistance to earlier generations of BTK inhibitors like ibrutinib. By irreversibly binding to the mutant kinase, BLU9931 restores pathway inhibition, thereby blocking abnormal B-cell receptor signaling that drives tumor proliferation and survival. It has shown promising activity in preclinical models of resistant chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and other B-cell cancers. Its selectivity reduces off-target effects, potentially improving safety and tolerability. BLU9931 is being investigated as a therapeutic option for patients who have relapsed or become refractory to prior BTK-targeted therapies, representing a key strategy in overcoming treatment resistance in hematologic malignancies.