While RC-3 was not as potent as NC-1 in BTK degradation, it did have a significant advantage in selectivity. The addition of the cyanoacrylamide with the geminal dimethyl group greatly diminished the reversible binding affinity (which was observed for other cyanoacrylamide inhibitors of BTK ), while maintaining potent covalent binding. This significantly reduced the activity against the noncovalent off targets LYN and CSK.