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A public-private partnership that supports the discovery of new medicines through open access research.
BI-9321 for NSD3This probe is available from Tocris, and Sigma The probe and its negative control are also available from opnMe.com. The control may be requested by clicking here. For any inquiries please contact proberequests@thesgc.org.group newOverview BI-9321 BI-9466 A collaboration between Boehringer Ingelheim and the SGC has resulted in the discovery of BI-9321, a potent and selective antagonist of the PWWP1 domain of NSD3. BI-9321 binds to the PWWP1 domain of NSD3 with a Kd of 166 nM by SPR and is selective over other PWWP domains including NSD2-PWWP1 and NSD3-PWWP2. BI-9321 antagonizes the interaction of H3 with NSD3-PWWP1 in U2OS cells as measured by NanoBRET with IC50 of 1.2 µM. A closely-related compound, BI-9466 is 200-fold less active and is a recommended negative control. Both compounds should be used in parallel in a dose response range between 0.1 and 20µM. Data relating to the discovery of this probe is being prepared for publication. In the meantime, in order to facilitate research by the community we are making this compound available through this website. Properties BI-9321 BI-9466 (negative control) Physical and chemical properties for BI-9321 Molecular weight 360.2 Molecular formula C22H21FN4 IUPAC name 4-(4-(amino-methyl)-2,6-dimethyl-phenyl)-5-(9-fluoro-2-aza-bicyclo[4.4.0]deca-1(6),2,4,7,9-pentaen-5-yl)-1-methyl-1H-imidazole MollogP 3.337 PSA 41.44 No. of chiral centres 0 No. of rotatable bonds 3 No. of hydrogen bond acceptors 3 No. of hydrogen bond donors 2 Physical and chemical properties for BI-9466 (Negative Control) Molecular weight 295.2 Molecular formula C17H21N5 IUPAC name 5-(5-(4-(amino-methyl)-2,6-dimethyl-phenyl)-3-methyl-3H-imidazol-4-yl)-1-methyl-1H-imidazole MollogP 0.7975 PSA 43.92 No. of chiral centres 0 No. of rotatable bonds 3 No. of hydrogen bond acceptors 3 No. of hydrogen bond donors 2 SMILES: BI-9321: Cc1cc(CN)cc(C)c1c1c(c2ccnc3cc(ccc23)F)n(C)cn1 BI-9466: Cc1cc(CN)cc(C)c1c1c(c2cncn2C)n(C)cn1 InChI: BI-9321: InChI=1S/C22H21FN4/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 BI-9466: InChI=1S/C17H21N5/c1-11-5-13(7-18)6-12(2)15(11)16-17(22(4)10-20-16)14-8-19-9-21(14)3/h5-6,8-10H,7,18H2,1-4H3 InChIKey: BI-9321: WOAOENGFAAUUGT-UHFFFAOYSA-N BI-9466: SFZHMKDAVPIXRB-UHFFFAOYSA-N Selectivity Profile Cell-based Assay Data Co-crystal structures Please wait whilst the interactive viewer is loaded! Main features 1. Predicted binding mode with H3K36me3 2. Overlay with BI-9321 structure 3. Zoomed BI-9321 structure showing hydrogen bonds References Böttcher, J., Dilworth, D., Reiser, U., Neumüller, R., Schleicher, M., & Petronczki, M. et al. (2019). Fragment-based discovery of a chemical probe for the PWWP1 domain of NSD3. Nature Chemical Biology. doi: 10.1038/s41589-019-0310-x
