Bruton's tyrosine kinase (BTK) is critical for the propagation of B-cell receptor signaling and is upregulated in many B-cell malignancies as compared with normal B-cells. BTK inhibition, both in vitro and in vivo, decreases proliferation and survival signals.⁷

Pirtobrutinib is an investigational, oral, highly selective (in preclinical studies, over 300-fold more selective for BTK vs 98% of 370 non-BTK-kinases), non-covalent (reversible) BTK inhibitor.^2,3 It possesses nanomolar potency independent of BTK C481 status in enzyme and cell-based assays.^2,3,6 Pirtobrutinib has been shown in preclinical studies to reversibly bind BTK, have high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and predominantly avoid off-target kinases.²