UNC1999

• CAT Number: I001657
• CAS Number: 1431612-23-5
• Molecular Formula: C₃₃H₄₃N₇O₂
• Molecular Weight: 569.74
• Purity: ≥95%
• Target: Histone Methyltransferase
• Solubility: 10 mM in DMSO
• Storage: Store at -20° C
• IC50: 2 nM(EZH2); 45 nM(EZH1)
• InChI: InChI=1S/C33H43N7O2/c1-7-8-24-15-23(6)37-33(42)28(24)19-35-32(41)27-16-26(17-30-29(27)20-36-40(30)22(4)5)25-9-10-31(34-18-25)39-13-11-38(12-14-39)21(2)3/h9-10,15-18,20-22H,7-8,11-14,19H2,1-6H3,(H,35,41)(H,37,42)
• InChIKey: DPJNKUOXBZSZAI-UHFFFAOYSA-N
• SMILES: CC1=CC(CCC)=C(CNC(C2=C(C=NN3C(C)C)C3=CC(C4=CN=C(N5CCN(C(C)C)CC5)C=C4)=C2)=O)C(N1)=O

UNC1999 (CAT: I001657) is a potent inhibitor of the lysine methyltransferases EZH2 (Enhancer of Zeste Homolog 2) and EZH1 (Enhancer of Zeste Homolog 1). It competitively binds to the SAM (S-adenosyl methionine) binding site of EZH2 and EZH1, inhibiting their enzymatic activity. UNC1999 exhibits high selectivity for EZH2 and EZH1 over other methyltransferases and non-epigenetic targets. It reduces the levels of the histone mark H3K27me3, which is associated with gene repression. In preclinical studies, UNC1999 has shown promise in prolonging the survival of mice with MLL-AF9 fusion-positive leukemia.

Reference

1: Katona BW, Liu Y, Ma A, Jin J, Hua X. EZH2 inhibition enhances the efficacy of
an EGFR inhibitor in suppressing colon cancer cells. Cancer Biol Ther.
2014;15(12):1677-87. doi: 10.4161/15384047.2014.972776. PubMed PMID: 25535899;
PubMed Central PMCID: PMC4622469.

2: Konze KD, Ma A, Li F, Barsyte-Lovejoy D, Parton T, Macnevin CJ, Liu F, Gao C,
Huang XP, Kuznetsova E, Rougie M, Jiang A, Pattenden SG, Norris JL, James LI,
Roth BL, Brown PJ, Frye SV, Arrowsmith CH, Hahn KM, Wang GG, Vedadi M, Jin J. An
orally bioavailable chemical probe of the Lysine Methyltransferases EZH2 and
EZH1. ACS Chem Biol. 2013;8(6):1324-34. doi: 10.1021/cb400133j. Epub 2013 Apr 24.
PubMed PMID: 23614352; PubMed Central PMCID: PMC3773059.