SW2_110A (SW2-110A) is a selective, cell-permeable inhibitor of chromobox homolog protein CBX8, binds CBX8 N-terminal chromodomain (ChD) with Kd of 800 nM.
SW2_110A displays > 5-fold selectivity for CBX8 ChD over all other CBX paralogs in vitro, binds to CBX2 with Kd of 4.6 uM.
SW2_110A specifically inhibits the association of CBX8 with chromatin in cells and inhibits the proliferation of THP1 leukemia cells driven by the MLL-AF9 translocation.
SW2_110A treatment results in the significant decrease in the expression of MLL-AF9 target genes, including HOXA9, validating the previously established role for CBX8 in MLL-AF9 transcriptional activation in THP1 cells.
Five chromobox (CBX) homolog proteins, CBX2,4,6,7,8, are incorporated into PRC1 complexes, where they mediate targeting to trimethylated lysine 27 of histone H3 (H3K27me3) via the N-terminal chromodomain (ChD). Individual CBX paralogs have been implicated as drug targets in cancer.