All compounds significantly induced apoptosis, to a comparable extent. The only exception is A6, which stayed on the level of vehicle control. This proves that the antiproliferative activity of 2 and 1j in MM.1S cells is based on the arrest of cell cycle and of induction of apoptosis. 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 probably. 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 2chloroacetic 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).