COMMENT Three days are required for reduction of H3K27me3 in MCF10a cells with IC50 ~135 nM.  I recommend using UNC1999 in parallel with its control, UNC2400, and the orthogonal probe, GSK343. Jun 16 2016 - 5:53pm; This probe is a dual inhibitor of EZH1 and EZH2 methyltransferase enzymes (in vitro IC50s are 45 nM and 4.6 nM, respectively), which are the components of Polycomb repressive complex 2. This complex converts dimethylated lysines into trimethylated lysines in H3K27. Trimethylation of K27 is a transcriptionally repressive epigenetic mark. The probe inhibits H3K27 trimethylation in MCF10A cells at 5 uM after 3 days treatment, shows toxicity after 7 days of treatment. Potential off-target effects could be due to the GPCR binding with Ki 4,700 nM; 65 nM; 300 nM; and 1,500 nM for Sigma1, Sigma 2, Histamine H3, and Norephedrine transporter, respectively. In vivo studies have shown that the probe has good PK properties; however, its inhibitory effect on EZH1 and EZH2 in different tissues has not been examined, and its organ and tissue distribution profiles were not reported. Therefore, if this probe is used for in vivo studies, careful investigation of its tissue and organ distribution are needed, as well as an analysis of its inhibitory effect of EZH1/2 and off-target GPCR receptors. I recommend using this probe along with UNC2400, which is a negative control molecule. Jun 30 2016 - 4:41am; UNC1999 has utility in cell-based experiments when used in conjunction with UNC2400.  Aug 29 2016 - 11:24pm; A concentration lower than 1 µM. The cellular IC50 for reduction of H3K27me3 levels is 124 nM. I would suggest 2-3x IC50 to avoid off-targets (e.g., GPCRs) at micromolar concentrations. Suggested to use UNC2400 as a control compound in parallel. A wider panel of off-targets (e.g., CEREP) would be required prior to in vivo use of this probe. Apr 19 2021 - 11:59am

MOA Protein substrate noncompetitive inhibitor;SAM competitive inhibitor

DESCRIPTION UNC1999 is a cell-permeable chemical probe for histone H3-lysine 27 (H3K27) methyltransferase EZH2 activity, developed by the Structural Genomics Consortium (SGC) in collaboration with the Center for Integrative Chemical Biology and Drug Discovery (CICBDD) at the University of North Carolina .
Click here to link to the SGC's full list of epigenetics probes. (GtoPdb)

DESCRIPTION UNC1999 is a SAM-competitive, potent and selective inhibitor of EZH2/1 with IC50s of <10 nM and 45 nM, repectively.

PRICE 106

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION Potent and selective EZH2/EZH1 inhibitor (Tocriscreen Plus)

DESCRIPTION Negative control of UNC 1999 (Cat. No. 4904) (Tocris Bioactive Compound Library)

DESCRIPTION UNC1999 is a orally bioavailable, effective and specific inhibitor of EZH2 (IC50=2 nM) and EZH1 (IC50=45). (TargetMol Bioactive Compound Library)