SML0778

UNC1999

≥98% (HPLC)

• Synonym(s): 1-Isopropyl-6-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-1H-indazole-4-carboxamide
• Empirical Formula (Hill Notation): C₃₃H₄₃N₇O₂
• CAS Number: 1431612-23-5
• Molecular Weight: 569.74
• MDL number: MFCD26960958
• UNSPSC Code: 41121800
• PubChem Substance ID: 329825598
• NACRES: NA.77

Properties

• Assay: ≥98% (HPLC)
• form: powder
• color: white to beige
• solubility: DMSO: 15 mg/mL, clear
• storage temp.: 2-8°C
• SMILES string: CC(C)N1CCN(C2=NC=C(C3=CC4=C(C=NN4C(C)C)C(C(NCC5=C(CCC)C=C(C)NC5=O)=O)=C3)C=C2)CC1
• 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)
• InChI key: DPJNKUOXBZSZAI-UHFFFAOYSA-N

Description

Biochem/physiol Actions

The polycomb repressive complex 2 (PRC2), which represses gene expression through methylation of histone H3 on lysine 27 (H3K27), contains either EZH1 or EZH2 as its catalytic subunit, with EZH1 being found in both dividing and non-dividing cells, whereas EZH2 is only found in actively dividing cells. UNC1999 is an orally bioavaliable selective inhibitor of both EZH2 and EZH1 lysine methyltransferases with IC₅₀ < 10 nM for EZH2 and 45 nM for EZH1. UNC1999 potently inhibited both wild-type and mutant Y641N EZH2 methyltransferase activity with less than a 5-fold difference in potency, and selectively killed diffused large B cell lymphoma (DLBCL) cells bearing Y641 point mutations. It was selective for EZH2 and EZH1 over 15 other lysine, arginine and DNA methyltransferases. UNC1999 is competitive with the cofactor S-adenosylmethionine (SAM) and non-competitive with the peptide substrate. Because it inhibits both EZH2 and EZH1, UNC1999 has potential advantages over EZH2 selective inhibitors in the disease settings where both PRC2 – EZH2 and PRC2 – EZH1 contribute to the methylation of H3K27.

For full characterization details, please visit the UNC1999 probe summary on the Structural Genomics Consortium (SGC) website.

UNC2400 is the negative control for the active probe, UNC1999. To request a sample of the negative control from the SGC, click here.

To learn about other SGC chemical probes for epigenetic targets, visit sigma.com/sgc

Features and Benefits

This compound is a featured product for Gene Regulation research. Click here to discover more featured Gene Regulation products. Learn more about bioactive small molecules for other areas of research at sigma.com/discover-bsm.

UNC1999 is an epigenetic chemical probe available through a partnership with the Structural Genomics Consortium (SGC). To learn more and view other SGC epigenetic probes, visit sigma.com/SGC.

Other Notes

UNC1999 has been expertly reviewed and recommended by the Chemical Probes Portal. For more information, please visit the UNC1999 probe summary on the Chemical Probes Portal website.

Safety Information

• Storage Class Code: 11 - Combustible Solids
• WGK: WGK 3
• Flash Point(F): Not applicable
• Flash Point(C): Not applicable