Lastly, we assessed the ability of the PROTACs to abrogate the activation of primary mouse B cells in response to B cell receptor stimulation. For this purpose, primary B cells were treated with anti-IgM for 18 hours , followed by staining for CD86, a B cell activation surface marker (Fig. ; Supp. Fig. ). The inhibition of B cell activation correlated well with the BTK degradation activity, with NC-1 and IR-2 showing the strongest effect, followed by RC-3 and RC-2. NC-1 and IR-2 displayed superior inhibition compared to Ibrutinib, underscoring the benefit of targeted degradation compared to inhibition alone. The cyanoacrylamides RC-3 and RC-2 required higher concentrations to reach maximal activity but also displayed superior activity to Ibrutinib at 1 µM.