BTK, a non-receptor intracellular kinase, belongs to the TEC family of tyrosine kinases and is an important part of the BCR signaling pathway. BTK protein consists of 659 amino acids and 5 domains (PH, TH, SH3, SH2, kinase domain), among which Y223 of the SH3 domain and Y551 of the kinase domain are two key tyrosine phosphorylation sites.

Covalent BTK inhibitors can irreversibly bind to C481 residues in the kinase domain. Non-covalent BTK inhibitors do not bind to C481 but inhibit BTK by binding with reversible non-covalent bonds, such as Fenebrutinib forming hydrogen bonds with K430, M477, and D539 residues.