UNC0642

UNC0642 is a potent, selective **small molecule inhibitor** of the histone methyltransferases **G9a (EHMT2)** and **GLP (EHMT1)**, which are enzymes responsible for mono- and dimethylation of lysine 9 on histone H3 (H3K9), a key epigenetic mark associated with transcriptional repression[1][3][4][6][9]. UNC0642 exhibits high enzymatic and cellular potency (IC50 <2.5 nM for enzyme, 110 nM cellular), strong selectivity over other protein methyltransferases and broad target classes, and favorable in vivo pharmacokinetics, making it an effective chemical probe for G9a/GLP-dependent biology[4][5][6][8][9]. The compound competitively inhibits the binding of substrate peptides to the G9a/GLP active site, resulting in decreased H3K9 methylation and subsequent activation of pro-apoptotic and tumor-suppressive gene expression programs, such as upregulation of TXNIP and oxidative stress pathways[1][3]. UNC0642 has been shown to induce apoptosis and suppress tumor growth in preclinical models of **breast cancer** and **bladder cancer**[1][3] and also to affect brain H3K9me2 levels in animal neurobiology studies[7]. It was developed as an improvement upon earlier G9a/GLP inhibitors, featuring lower cytotoxicity and improved in vivo potency and selectivity[8][9].

Other names

UNC 0642UNC0642UNC-06422-(4,4-difluoropiperidin-1-yl)-N-(1-isopropylpiperidin-4-yl)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazolin-4-amine2-(4,4-difluoro-1-piperidinyl)-6-methoxy-N-[1-(1-methylethyl)-4-piperidinyl]-7-[3-(1-pyrrolidinyl)propoxy]-4-quinazolinamine