Compound name
BI-9321
Protein family
Methyltransferase
Target name
NSD3@PWWP1
Affinity biochemical (nM)
203
Affinity on-target cellular (nM)
1400
CG-Set
Epigenetic set
Recommended Concentration
1 µM
Compound EUbOPEN ID
EUB0000269b
SMILES
Cc1cc(CN)cc(C)c1-c1ncn(C)c1-c1ccnc2cc(F)ccc12
InChIKey
WOAOENGFAAUUGT-UHFFFAOYSA-N
Mode of action
Inhibitor
Negative control
BI-9466
Affinity biochemical definition
IC50
Affinity biochemical assay type
TR-FRET binding assay (NSD3-PWWP1)
Affinity Biochemical Source Knowledge
https://www.nature.com/articles/s41589-019-0310-x
Affinity biochemical relation
=
Affinity on-target cellular definition
IC50
Affinity on-target cellular assay type
NanoBRET assay (Nluc-NSD3-PWWP1 fusion protein in U2OS cells)
Affinity on-target cellular source knowledge
https://www.nature.com/articles/s41589-019-0310-x
Affinity on-target cellular relation
=
Selectivity platform
PWWP domain panel (DSF assays, literature)
Selectivity platform number of targets
14
Selectivity remarks
Screened against 14 PWWP domains (DSF assays): dTm(NSD3@PWWP1) = 5.5 K, dTm(ZCWPW1@PWWP) <2 K, dTm(PSIP@PWWP) <2 K, dTm(NSD3@PWWP2) <2 K, dTm(NSD2@PWWP1) <2 K, dTm(MUM1@PWWP) <2 K, dTm(MSH6@PWWP) <2 K, dTm(HDGFRP3@PWWP) <2 K, dTm(HDGFR2@PWWP) <2 K, dTm(GLYR1@PWWP) <2 K, dTm(DNMT3B@PWWP) <2 K, dTm(DNMT3A@PWWP) <2 K, dTm(BRPF3@PWWP) <2 K, dTm(BRPF2@PWWP) <2 K, dTm(BRD@PWWP) <2 K; In-vitro potency of closest targets (ITC experiment): Kd(NSD2@PWWP1) >10 µM, Kd(NSD3@PWWP2) >10 µM, https://www.nature.com/articles/s41589-019-0310-x; Screened at 500 µM against 10 PWWP, 4 WD40, 3 Tudor, and 4 MBT domains of 20 proteins (DSLS measurements): dTagg(NSD3@PWWP1) = 3.8 K, dTagg(NSD2@PWWP1) = 0.6 K, dTagg(NSD3@PWWP2) = -0.6 K, dTagg(BRPF1@PWWP) = 0.3 K, dTagg(BRD1@PWWP) = -1.7 K, dTagg(BRPF3@PWWP) = 0.4 K, dTagg(ZCWPW1@PWWP) = 0.1 K, dTagg(DNMT3A@PWWP1) = 0.1 K, dTagg(DNMT3B@PWWP1) = 0.1 K, dTagg(MSH6@PWWP) = -0.1 K, dTagg(WDR20@PWWP) = -0.2 K, dTagg(WDR5@PWWP) = - 1.5 K, dTagg(WDR48@PWWP) = -0.1 K, dTagg(EED@PWWP) = 0.2 K, dTagg(53BP1@PWWP1) = 0.0 K, dTagg(SETDB1@PWWP) = 0.2 K, dTagg(TDRD3@PWWP) = 0.5 K, dTagg(L3MBTL3@PWWP) = 0.0 K, dTagg(L3MBTL1@PWWP1) = 0.0 K, dTagg(SCML2@PWWP1) =0.0 K, https://www.nature.com/articles/s41589-019-0310-x; Screened at 10 µM against 31 kinases (SelectScreen® Kinase Profiling), closest targets as % of inhibition: IGF1R (23%), PRKACA (18%), CHEK1 (17%), https://www.nature.com/articles/s41589-019-0310-x; Screened at 1 µM and 10 µM against 34 protein, RNA and DNA methyltransferases, and EP300 (acetyltransferase): highly selective with >80% remaining activity on all proteins tested, https://www.nature.com/articles/s41589-019-0310-x; Screened at 10 µM quantitative chemical proteomics in high-salt chromatin extracts of Cal-120 cells: clean selectivity profile, with closest targets KDM1B and BRD4(BD1); In-vitro potency of closest targets (AlphaLisa assays): IC50(KDM1B) >100 µM, IC50(BRD4) >100 µM, https://www.nature.com/articles/s41589-019-0310-x; Screened at 100 µM against 48 bromodomains (DSF assay): clean selectivity profile with all targets dTm <2K, https://www.nature.com/articles/s41589-019-0310-x;
Selectivity Source Knowledge
https://www.nature.com/articles/s41589-019-0310-x
Selectivity Number of Off-targets
0