selectively degraded HDAC6 without significant effects on the other HDAC isoforms, as previously reported. By utilizing DCAF11 instead of CRBN for HDAC degradation, 1j and 2 are able to broaden the scope of degraded HDAC isoforms, degrading not only HDAC6 but also HDAC1, 2, 4 and 6. In addition, the degradation pattern of 1j was further investigated by its time dependency. This analysis revealed less differences between the DCAF11-recruiting PROTACs and the HDACi. Synthesis and evaluation of the non-degrading control 1j-nc. In the next step, we wanted to design and synthesize a non-degrading control for the most effective PROTAC 1j. It is essential that the non-degrading control is as comparable to the PROTAC as possible, without binding to the E3 ligase. By the absence of degradation, the non-degrading control proves TPD, which requires the E3 ligase for the reduction of protein levels. In addition, it enables to distinguish between inhibitor and degrader effects. In case of 1j the non-degrading control was designed by substituting the electrophilic warhead of the DCAF11 ligand. The replacement of 2-chloroacetic acid by propionic acid led to no successful U-4CR, because of reduced nucleophilicity of the propionic acid. We successfully obtained the U-4CR product bound on resin by switching to formic acid. After cleavage and purification, as described before, 1j-nc was prepared in 38% yield over seven steps (Scheme 2).