YX968 is a potent, selecive HDAC3/8 dual PROTAC degrader with DC50 of 1.7 and 6.1 nM in degrading HDAC3 and HDAC8 respectively (MDA-MD-231 cell, 8 h).
YX968 induces highly potent, rapid, and selective degradation of both HDAC3/8 without triggering pan-HDAC inhibitory effects.
YX968 shows HDAC1 and HDAC3 enzyme inhibition (IC50 = 591 nM and 284 nM, respectively).
YX968 rapidly degrades HDAC3 and HDAC8 via the ubiquitin-proteasome system (UPS).
YX968 is highly specific in targeted HDAC3/8 degradation, with no effect on HDAC2, HDAC4, HDAC6, and HDAC7.
YX968 does not significantly alter transcriptome.
YX968 is highly potent on suppressing the growth of cancer cell lines, YX968 (125 nM) estrogen receptor-positive BC cell lines MCF7 and T47D as well as the TNBC cell lines BT549, MDA-MB-468 and HCC1806.
