Fig. 4
From: Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies
Mechanisms for the action of representative BTK inhibitors. a Chemical structure of the covalent BTK inhibitor ibrutinib. b Chemical structure of the non-covalent BTK inhibitor ARQ 531. c Ibrutinib covalently binds to BTK cysteine 481 (C481), competes with ATP in the ATP binding pocket, and inhibits autophosphorylation of BTK. The action of ibrutinib requires its binding to BTK C481, and BTK C481 mutations abrogate the binding of ibrutinib and lead to the resistance to ibrutinib. d ARQ 531 non-covalently interacts with BTK, occupies the ATP binding pocket, and inhibits BTK autophosphorylation. The effect of ARQ 531 does not require its binding to BTK C481. Therefore, ARQ 531 remains active in patients with BTK C481 mutations. c, d were made by using PyMOL 0.99