BI-9321 (hydrochloride)

BI-9321 is an antagonist of the histone-lysine N-methyltransferase NSD3 (IC50 = 0.203 µM in a time-resolved FRET (TR-FRET) assay). It selectively binds to the NSD3 PWWP1 domain over 14 other PWWP domains, including NSD2-PWWP1 and NSD3-PWWP2, at 100 µM. BI-9321 is also selective for NSD3 over 20 methyllysine-binding proteins in differential static light scattering (DSLS) assays at 500 µM, 35 DNA or RNA methyltransferases in enzyme activity assays at 10 µM, and 31 kinases in enzyme activity assays at 10 µM. It decreases expression of mRNA encoding Myc in MOLM-13 acute myeloid leukemia (AML) cells when used at a concentration of 10 µM for six hours and reduces the viability of MOLM-13 cells after six days (IC50 = 26.8 µM). InChI: InChI=1S/C22H21FN4.3ClH/c1-13-8-15(11-24)9-14(2)20(13)21-22(27(3)12-26-21)18-6-7-25-19-10-16(23)4-5-17(18)19,,,/h4-10,12H,11,24H2,1-3H3,3*1H InChIKey: DCDXMBVQCRHZMW-UHFFFAOYSA-N SMILES: FC1=CC2=C(C(C3=C(C4=C(C)C=C(CN)C=C4C)N=CN3C)=CC=N2)C=C1.Cl.Cl.Cl