MS132 is a highly potent and selective VHL-recruiting WDR5 PROTAC degrader with DC50 of 92 nM in MIA PaCa-2 cells.
MS132 shows high binding affinities to both VCB E3 ligase (KD= 534 ± 48 nM) and WDR5 (KD= 122 ± 56 nM) in ITC assays.
MS132 induces WDR5 degradation in a concentration-, time-, and UPS-dependent manner in PDAC cells.
MS132 exhibits antiproliferative activity in multiple PDAC cell lines including MIA PaCa-2, BxPC-3, HPAF-II, Panc10.05, and PANC-1, with GI50 of 4-32 uM.
MS132 has the potential to be used in in vivo animal studies.
