UNC0638

SKU: orb1226666

Description

A potent, selective, substrate-competitive inhibitor of G9a (EHMT2) and GLP (EHMT1) with IC50 of <15 nM and 19 nM in SAHH-coupled assays, respectively; very weak activity against JmjD2E and DNMT1; inactive against EZH2, SETD7, DOT1L and SETD8; reduces the clonogenicity of MCF7 cells and the abundance of H3K9me2.

Key Properties

• CAS Number: 1255580-76-7
• MW: 509.7265
• Purity: >98% (HPLC)
• Formula: C₃₀H₄₇N₅O₂
• SMILES: COC1=CC2=C(NC3CCN(C(C)C)CC3)N=C(C4CCCCC4)N=C2C=C1OCCCN5CCCC5
• Target: HMTase
• Solubility: DMSO: ≥ 30 mg/mL

Bioactivity

• In Vitro:
  UNC0638, an inhibitor of G9a and GLP with excellent potency and selectivity over a wide range of epigenetic and non-epigenetic targets. The Ki of UNC0638 is determined to be 3.0±0.05 nM (n=2). Consistent with this, the Morrison Ki for UNC0638 is 3.7±0.2 nM (n=3). The selectivity of UNC0638 over a wide range of epigenetic targets is evaluated. Notably, UNC0638 is inactive against other H3K9 (SUV39H1 and SUV39H2), H3K27 (EZH2), H3K4 (SETD7, MLL and SMYD3), H3K79 (DOT1 L) and H4K20 (SETD8) methyltransferases, as well as PRDM1, PRDM10 and PRDM12. In addition, UNC0638 is inactive against protein arginine methyltransferases PRMT1 and PRMT3, and HTATIP, a histone acetyltransferase. Of note, UNC0638 has weak but measurable activity against JMJD2E (IC50 = 4, 500±1, 100 nM), a Jumonji protein demethylase and DNA methyltransferase DNMT1 (IC50 = 107, 000±6, 000 nM). Nevertheless, the selectivity of UNC0638 for G9a and GLP over JMJD2E is >200-fold, and selectivity for G9a and GLP over DNMT1 is >5, 000-fold. UNC0638 is a type of small molecule that can specifically inhibit the enzyme activity of histone methyltransferase EHMT and reduce the H3K9 dimethylation (H3K9me2) levels in cells.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

UNC 0638 | UNC-0638

Quick Database Links

Gene Symbol

HMTase