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UNC 0646 G9a and GLP inhibitor

Catalog No.A4504
Size Price Stock Qty
10mM (in 1mL DMSO)
$120.00
In stock
5mg
$60.00
In stock
10mg
$105.00
In stock
50mg
$350.00
In stock

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Sample solution is provided at 25 µL, 10mM.

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Chemical structure

UNC 0646

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Chemical Properties

Cas No. 1320288-17-2 SDF Download SDF
Chemical Name N-(1-cyclohexylpiperidin-4-yl)-6-methoxy-7-(3-piperidin-1-ylpropoxy)-2-(4-propan-2-yl-1,4-diazepan-1-yl)quinazolin-4-amine
Canonical SMILES CC(C)N1CCCN(CC1)C2=NC3=CC(=C(C=C3C(=N2)NC4CCN(CC4)C5CCCCC5)OC)OCCCN6CCCCC6
Formula C36H59N7O2 M.Wt 621.9
Solubility >24.1mg/mL in DMSO Storage Store at 4°C
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
Shipping Condition Evaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request

Background

IC50: 6 nm (G9a IC50); 26 nm (Cellular IC50); 3.3 μM (Cell toxicity EC50)

Histone-lysine N-methyltransferase, H3 lysine-9 specific 3, also known as euchromatic histone-lysine N-methyltransferase 2 (EHMT2) and G9a, is a histone methyltransferase that in humans is encoded by the EHMT2 gene. Protein lysinemethyltransferase G9a plays key roles in the transcriptional repression of a variety of genes via dimethylation of lysine 9 on histoneH3 (H3K9me2) of chromatin as well as dimethylation of nonhistone proteins including tumor suppressor p53.

In vitro: UNC0646 is reported to be a potent and selective inhibitor of the homologous protein lysine methyltransferases, G9a and GLP (IC50 values are 6 nM and 15 nM for G9a and GLP, respectively). UNC0646 also potently blocks G9a/GLP methyltransferase activity in cells (IC50 = 10 nM in MCF7 cells) and exhibits low cellular toxicity (EC50 = 4.7 μM in MCF7 cells). UNC0646 is selective for G9a/GLP over a range of other protein lysine methyltransferases and protein arginine methyltransferases [1].

In vivo: The authors previously discovered potent and selective G9a/GLP inhibitors including the cellular chemical probe UNC0638, which displays an excellent separation of functional potency and cell toxicity. However, this inhibitor is not suitable for animal studies due to its poor pharmacokinetic (PK) properties. In this study, the authors report the discovery of the first G9a and GLP in vivo chemical probe UNC0642, which not only maintains high in vitro and cellular potency, low cell toxicity, and excellent selectivity, but also displays improved in vivo PK properties, making it suitable for animal studies [2].

References:
[1] Liu F, Barsyte-Lovejoy D, Allali-Hassani A, He Y, Herold JM, Chen X, Yates CM, Frye SV, Brown PJ, Huang J, Vedadi M, Arrowsmith CH, Jin J.  Optimization of cellular activity of G9a inhibitors 7-aminoalkoxy-quinazolines. J Med Chem. 2011;54(17):6139-50.
[2] Liu F, Barsyte-Lovejoy D, Li F, Xiong Y, Korboukh V, Huang XP, Allali-Hassani A, Janzen WP, Roth BL, Frye SV, Arrowsmith CH, Brown PJ, Vedadi M, Jin J.  Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP. J Med Chem. 2013;56(21):8931-42.