Quantitive chemoproteomic investigation. To investigate the effects of 17c on the global proteome, a chemoproteomic investigation by quantitative diaPASEF-based mass spectrometry in MM.1S cells was conducted. In total, 5738 proteins were identified and among them, seven Zn 2+ -dependent HDAC isoforms were found. The volcano plot in Figure shows that HDAC6 was significantly reduced in 17c-treated cells compared to vehicle-treated cells. Additionally, degradation of IKZF3, a CRBN neosubstrate, as well as collateral degradation of MIER1, a part of an HDAC1/2 multienzyme complex, was observed upon 17c treatment. The degradation of MIER1 has also been observed in previous chemoproteomic investigations of a HDAC-focused degrader library. The degradation of other HDAC isoforms was not observed (Figure ). Thus, the HDAC6-selective degradation over other HDAC isoforms, as shown by immunoblotting, could be confirmed.