New PROTAC derivatives inhibited WT and mutated BTK with high selectivity; particularly, the most active molecules resulted in PROTAC 5 (Figure 13), which strongly causes BTK-WT and BTK-C481S degradation, and the inhibition of BTK-WT and BTK-C481S TMD8 cell proliferation; in addition, it showed moderate membrane permeability and good plasma stability, providing a basis for developing new and potent reversible non-covalent PROTAC-based therapeutic molecules able to treat B-cell lymphomas in particular [12]. Here, BTK is linked to B-cell non-Hodgkin lymphoma.