Home Epigenetics Histone Methyltransferase inhibitor - G9a/GLP inhibitor UNC0642 For research use only.

UNC0642

UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.

UNC0642 Chemical Structure

UNC0642 Chemical Structure

CAS No. 1481677-78-4

Purity & Quality Control

UNC0642 Related Products

Signaling Pathway

Histone Methyltransferase Signaling Pathways

Histone Methyltransferase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
PANC1 Function assay Inhibition of lysine methyltransferase G9a in human PANC1 cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay, IC50 = 0.04 μM. 24102134
MDA-MB-231 Function assay Inhibition of lysine methyltransferase G9a in human MDA-MB-231 cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay, IC50 = 0.11 μM. 24102134
PC3 Function assay Inhibition of lysine methyltransferase G9a in human PC3 cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay, IC50 = 0.13 μM. 24102134
U2OS Function assay Inhibition of lysine methyltransferase G9a in human U2OS cells assessed as reduction of H3K9me2 cellular level by immunofluorescence in-cell Western assay, IC50 = 0.13 μM. 24102134
PANC1 Cytotoxicity assay 48 hrs Cytotoxicity against human PANC1 cells after 48 hrs by Alamar Blue assay, EC50 = 3.5 μM. 24102134
U2OS Cytotoxicity assay 48 hrs Cytotoxicity against human U2OS cells after 48 hrs by Alamar Blue assay, EC50 = 6 μM. 24102134
PC3 Cytotoxicity assay 48 hrs Cytotoxicity against human PC3 cells after 48 hrs by Alamar Blue assay, EC50 = 8.9 μM. 24102134
MDA-MB-231 Cytotoxicity assay 48 hrs Cytotoxicity against human MDA-MB-231 cells after 48 hrs by Alamar Blue assay, EC50 = 16.7 μM. 24102134
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Biological Activity

Description UNC0642 is a potent, selective inhibitor of histone methyltransferases G9a/GLP with IC50s less than 2.5 nM for G9a and GLP and shows more than 300-fold selective for G9a and GLP over a broad range of kinases, GPCRs, transporters, and ion channels.
Targets
G9a [1]
(Cell-free assay)		 GLP [1]
(Cell-free assay)
<2.5 nM <2.5 nM
In vitro
In vitro UNC0642 is competitive with the peptide substrate and non-competitive with the cofactor SAM. The Ki of UNC0642 is determined to be 3.7 ± 1 nM. It is more than 20,000-fold selective for G9a and GLP over 13 other methyltransferases (IC50 > 50,000 nM) and more than 2,000-fold selective over PRC2-EZH2 (IC50 > 5,000 nM). UNC0642 displays high potency (IC50 < 150 nM) in reducing cellular levels of H3K9me2, low cell toxicity (EC50 > 3,000 nM), resulting in a good separation of functional potency and cell toxicity with a tox/function ratio (which is determined by dividing the EC50 value of the observed toxicity by the IC50 value of the functional potency) of > 45 in U2OS, PC3, and PANC-1 cells. UNC0642 reduces clonogenicity in PANC-1 cells in a concentration-dependent manner while it has no effect on clonogenicity in MDA-MB-231 cells[1].
Cell Research Cell lines MDA-MB-231, PC3, and U2OS cells
Concentrations --
Incubation Time 48 h
Method

MDA-MB-231, PC3, and U2OS cells are cultured in RPMI with 10% FBS, PANC-1 cells in DMEM with 10% FBS. Cells are treated with inhibitors for 48 h. Cell viability assays are performed by incubating cells with 0.1 mg/mL of resazurin for 3-4 h. Resazurin reduction is monitored with 544 nm excitation, measuring fluorescence at 590 nm.
Experimental Result Images Methods Biomarkers Images PMID
Growth inhibition assay Cell viability 28630300
Western blot G9A / di-mH3K9 / ERBB3 31619200
In Vivo
In vivo For evaluation in vivo PK properties in male Swiss Albino mice, a single intraperitoneal (IP) injection (5 mg/kg) of UNC0642 results in a plasma Cmax (maximum concentration) of 947 ng/mL and an AUC (area under the curve) of 1265 hr*ng/mL. It displays modest brain penetration with a brain/plasma ratio of 0.33[1]. A single intraperitoneal (i.p.) injection dose of 5 mg/kg of UNC0642 is sufficient to inhibit G9a activity in adult mice. UNC0642 improves the life span and weight gain of m+/pΔS−U pups, produces long-lasting activation of PWS-associated genes, is apparently well tolerated and produces no notable acute toxicity, and does not interfere with the expression of the AS-associated Ube3a gene[2].
Animal Research Animal Models male Swiss Albino mice
Dosages 5 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 546.7 Formula

C29H44F2N6O2
CAS No. 1481677-78-4 SDF Download UNC0642 SDF
Smiles CC(C)N1CCC(CC1)NC2=NC(=NC3=CC(=C(C=C32)OC)OCCCN4CCCC4)N5CCC(CC5)(F)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (182.91 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 100 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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