BI-9321 trihydrochloride (BI 9321) is a potent, selective and cellular active inhibitor of the NSD3-PWWP1 domain with SPR Kd of 166 nM.
BI-9321 displays no significant inhibition against a selection of 31 diverse kinases, closest family members NSD2-PWWP1, BRD4 and KDM1B.
BI-9321 targets the methyl-lysine binding site of the PWWP1 domain with sub-micromolar in vitro activity and cellular target engagement at 1 uM.
BI-9321 downregulated Myc messenger RNA expression and reduces proliferation in MOLM-13 cells, BI-9321 inhibited proliferation of both MOLM-13 (IC50=26.8 uM) and RN2 cells (IC50=13 uM).
BI-9321 enhanced the JQ1-dependent proliferation phenotype in the MOLM-13 cell line.
