1. Epigenetics
    Autophagy
  2. Histone Methyltransferase
    Autophagy

UNC0638 

Cat. No.: HY-15273 Purity: 98.60%
Data Sheet SDS Handling Instructions

UNC0638 is a potent G9a (EHMT2) (IC50<15 nM) and GLP (EHMT1) inhibitor (IC50=19 nM) in S-adenosyl-L-homocysteine hydrolase (SAHH)-coupled assays.

For research use only. We do not sell to patients.
UNC0638 Chemical Structure

UNC0638 Chemical Structure

CAS No. : 1255580-76-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $67 In-stock
5 mg $60 In-stock
10 mg $90 In-stock
50 mg $250 In-stock
100 mg $440 In-stock
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500 mg   Get quote  

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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

UNC0638 is a potent G9a (EHMT2) (IC50<15 nM) and GLP (EHMT1) inhibitor (IC50=19 nM) in S-adenosyl-L-homocysteine hydrolase (SAHH)-coupled assays.

IC50 & Target

IC50: <15 nM (G9a), 19±1 nM (GLP)[1]

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 (DOT1L) 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[1]. 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[2].

References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 1 mg 5 mg 10 mg
1 mM 1.9618 mL 9.8091 mL 19.6182 mL
5 mM 0.3924 mL 1.9618 mL 3.9236 mL
10 mM 0.1962 mL 0.9809 mL 1.9618 mL
Kinase Assay
[1]

The enzymatic reactions are conducted in duplicate at room temperature for 1 hour in a 50 μL mixture containing PKMT assay buffer, substrate coated plate, 10 M SAM, a HMT enzyme (EZH2 (800 ng/reaction), MLL (300 ng/reaction), PRMT1 (0.5 ng/reaction), SUV39H1 (75 ng/reaction) and UNC0638 (0-1.25 μM). After enzymatic reactions, 100 μL of first antibody is added to each well and the plate is incubated at room temperature for an additional 1 h. 100 μL of secondary antibody is added to each well and the plate is incubated at room temperature for an additional 30 min. 100 μL of developer reagents are added to wells and luminescence is measured using a BioTek SynergyTM 2 microplate reader. Enzyme activity assays are performed in duplicates at each concentration. The luminescence data are analyzed using the computer software, Graphpad Prism[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

UNC0638 is dissolved in deuterated DMSO (10 mM) and deuterated H2O (90:10 ratio)[1].

MDA-MB-231, PC3, HCT116 cells are cultured in RPMI with 10% FBS, 22RV1 cells in alphaMEM and 10% FBS, MCF7 and IMR90 cells in DMEM with 10% FBS. Cells are grown in the presence or absence of UNC0638 (10 nM, 100 nM, 1 μM, 10 μM, and 100 μM ) for stated amount of time. The media is removed and replaced with DMEM 10% FBS without phenol red supplemented with 1mg/mL of MTT and incubated for 1-2 h. Live cells reduce yellow MTT to purple formazan. The resulting formazan is solubilized in acidified isopropanol and 1% Triton and absorbance measured at 570 nm, corrected for 650 nm background[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

UNC0638 is dissolved in DMSO and then diluted in water or PBS (Mice)[1].

Mice[1]
Standard DMPK studies in male Swiss albino mice (3 animals per data point) are conducted, following intravenous (IV, 1 mg/kg), oral (PO, 3 mg/kg), and intraperitoneal (IP, 2.5 mg/kg) administration of UNC0638. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

509.73

Formula

C₃₀H₄₇N₅O₂

CAS No.

1255580-76-7

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 30 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 98.60%

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Product Name:
UNC0638
Cat. No.:
HY-15273
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