PF-303 is a potent, oral inhibitor of Bruton's tyrosine kinase ( BTK ) ( IC 50 =0.64 nM). The melamine portion of PF-303 forms a covalent bond with BTK's Cys481, which is reversible and exhibits a high selectivity compared to irreversible covalent BTK inhibitors. PF-303 can be used to model and study the effects of BTK inhibition on the mature immune system, including effects on B-cell subsets, antibody responses, and T-cell-mediated activation.