In vitro Activity Assays for BTK (Carried out by Nanosyn, Santa Clara, CA) Test compounds were diluted in DMSO to a final concentration that ranged from 2 µM to 11.3 pM, while final concentration of DMSO in all assays was kept at 1%. The compounds were incubated with BTK for 2 hours in a 2x buffer containing the following: 1.2 nM BTK, 100 mM HEPES pH = 7.5, 10 mM MgCl2, 2 mM DTT, 0.1% BSA, 0.01% Triton X-100, 20 µM Sodium Orthovanadate and 20 µM Beta-Glycerophosphate. Reaction was initiated by twofold dilution into a solution containing 5 µM ATP (50 µM for C481S) and substrate. The reference compound Staurosporine was tested in a similar manner.