YX862 is a highly potent and selective hydrazide-based HDAC8-PROTAC degrader with DC50 values of 2.6 nM in MDA-MB-231 and 1.8 nM in MCF-7 cells.
YX862 does not degrade HDAC1 and HDAC2, and HDAC3.
The proteasome inhibitor MG132 or the neddylation inhibitor MLN4924 blocks the degradation of HDAC8 by YX862.
Degradation of HDAC8 by YX862 triggers SMC3 hyperacetylation in MDA-MB-231 cells, without significantly triggering histone post-translational modification (PTM).
YX862 dose-dependently inhibited cell proliferation of SU-DHL-2 cells (IC50 = 0.72 μM), while PCI-34051 was less effective (IC50 > 5.0 μM).
