Inhibitors, Agonists, Screening Libraries
www.MedChemExpress Data Sheet
BIOLOGICAL ACTIVITY:
UNC0638 is a potent G9a (EHMT2) (IC 50<15 nM) and GLP (EHMT1) inhibitor (IC 50=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
哑光玻璃non–epigenetic targets.The K i of UNC0638 is determined to be 3.0±0.05 nM (n=2). Consistent with this, the Morrison K i 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 (IC 50=4,500±1,100 nM), a
智能控制
模块Jumonji protein demethylase and DNA methyltransferase DNMT1 (IC 50=107,000±6,000 nM). Nevertheless, the selectivity of气囊
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 H3K9dimethylation (H3K9me2) levels in cells [2].
PROTOCOL (Extracted from published papers and Only for reference)
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 (0.5ng/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].
Cell Assay: UNC0638 is dissolved in deuterated DMSO (10 mM) and deuterated H2O (90:10 ratio)[1].[1]MDA–MB–231, PC3, HCT116cells 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].
Animal Administration: UNC0638 is dissolved in DMSO and then diluted in water or PBS (Mice)[1].[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
Product Name:
UNC0638Cat. No.:
HY-15273CAS No.:
j biol chem1255580-76-7Molecular Formula:
C 30H 47N 5O 2Molecular Weight:
509.73Target:
Histone Methyltransferase; Autophagy Pathway:
Epigenetics; Autophagy Solubility:
谷氨酸发酵
(PO, 3 mg/kg), and intraperitoneal (IP, 2.5 mg/kg) administration of UNC0638.
References:
[1]. Vedadi M, et al. A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol. 2011 Jul 10;7(8):566–74.
[2]. Fu L, et al. Effects of the Histone Methyltransferase Inhibitor UNC0638 on Histone H3K9 Dimethylation of Cultured Ovine Somatic Cells and Development of Resulting Early Cloned Embryos. Reprod Domest Anim. 2014 Apr;49(2):e21–5.
Caution: Product has not been fully validated for medical applications. For research use only.
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