Roman Belle, Hilal Saraç, Eidarus Salah, Bhaskar Bhushan, Aleksandra Szykowska, Grace Roper, Anthony Tumber, Skirmantas Kriaucionis, Nicola Burgess-Brown, Christopher J Schofield, Tom Brown, Akane Kawamura
Ten-eleven translocation enzymes (TETs) are Fe(II)/2-oxoglutarate (2OG) oxygenases that catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in eukaryotic DNA. Despite their roles in epigenetic regulation, there is a lack of reported TET inhibitors. The extent to which 2OG oxygenase inhibitors, including clinically used inhibitors and oncometabolites, modulate DNA modifications via TETs has been unclear. Here, we report studies on human TET1-3 inhibition by a set of 2OG oxygenase-focused inhibitors, employing both enzyme-based and cellular assays...
January 31, 2024: Journal of Medicinal Chemistry