Small Molecule Inhibitors of TET Dioxygenases: Bobcat339 Activity Is Mediated by Contaminating Copper(II).

ABSTRACT: Ten eleven translocation (TET) dioxygenases 1-3 are non-heme Fe(II) and α-ketoglutarate dependent enzymes that catalyze oxidation of 5-methylcytosine (5mC) in DNA to hydroxymethyl-C, formyl-C, and carboxy-C. This typically leads to gene activation and epigenetic remodeling. Most known inhibitors of TET are α-ketoglutarate mimics that may interfere with other α-ketoglutarate dependent enzymes. Recently, a novel cytosine-based inhibitor of TET, Bobcat339, was reported to have mid-μM inhibitory activity against TET1 and TET2. The molecule is now sold as a TET inhibitor by several vendors. We independently prepared Bobcat339 in our laboratory and observed that it had minimal inhibitory activity against human TET1 and TET2 via a quantitative LC-ESI-MS/MS assay. Furthermore, the inhibitory activ

SUBMITTER: Weirath NA 

PROVIDER: S-EPMC9109264 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature