1320288-17-2

G9a and G9a-like protein (GLP) are euchromatic histone-lysine methyltransferases (EHMT2 and EHMT1, respectively) that can heterodimerize with each other to methylate several proteins in addition to histone H3. UNC0646 is a potent and selective inhibitor of G9a and GLP activities in vitro (IC₅₀s = 6 and 15 nM, respectively) and G9a/GLP-mediated dimethylation of histone 3 on lysine 9 in MDA-MB-231 cells (IC₅₀ = 26 nM). It is highly selective for G9a/GLP over several other protein lysine and arginine methyltransferases. UNC0646 potently inhibits G9a/GLP activity in a variety of cancer cell lines as well as in the human fetal lung IMR-90 line. This compound selectively targets the corepressor function of G9a without affecting its ability to act as a coactivator with glucocorticoid receptor.

UNC0646 is a novel Protein lysine methyltransferase G9a inhibitor.

ChEBI: N-(1-cyclohexyl-4-piperidinyl)-6-methoxy-7-[3-(1-piperidinyl)propoxy]-2-(4-propan-2-yl-1,4-diazepan-1-yl)-4-quinazolinamine is a member of quinazolines.

G9a: 6 nM (IC₅₀); GLP: <15 nM (IC₅₀)

+4°C

[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.