BI-9321

BI-9321 for NSD3

This 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.

overview
Probe Negative control

 

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
Probe Negative control
BI-9321

 

BI-9466

BI-9321

 

BI-9466

Physical and chemical properties for BI-9321
Molecular weight360.2
Molecular formulaC22H21FN4
IUPAC name4-(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
MollogP3.337
PSA41.44
No. of chiral centres0
No. of rotatable bonds3
No. of hydrogen bond acceptors3
No. of hydrogen bond donors2
Physical and chemical properties for BI-9466 (Negative Control)
Molecular weight295.2
Molecular formulaC17H21N5
IUPAC name5-(5-(4-(amino-methyl)-2,6-dimethyl-phenyl)-3-methyl-3H-imidazol-4-yl)-1-methyl-1H-imidazole
MollogP0.7975
PSA43.92
No. of chiral centres0
No. of rotatable bonds3
No. of hydrogen bond acceptors3
No. of hydrogen bond donors2

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

in vitro potency
cell based assay data

references
pk properties
co-crystal structures

Main features

  • Predicted binding mode with H3K36me3
  • Overlay with BI-9321 structure
  • Zoomed BI-9321 structure showing hydrogen bonds
synthetic schemes
materials and methods