Bobcat 339 is a cytosine derivative that was originally found to be an inhibitor of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) and TET2 (IC50s = 33 and 73 ?M, respectively, in cell-free assays).1 However, it was found that the TET inhibitory activity was due to residual copper in the Bobcat 339 preparation used for the experiments.2 Copper-containing Bobcat 339 (10 ?M) also reduces DNA 5-hydroxymethylcytosine (5-hmC) levels in HT22 hippocampal neurons, but copper-free preparations of Bobcat 339 (50 ?M) do not reduce DNA 5-hmC levels in Hep3B cells.1,2
1.Chua, G.N.L., Wassarman, K.L., Sun, H., et al.Cytosine-based TET enzyme inhibitorsACS Med. Chem. Lett.10(2)180-185(2019) 2.Weirath, N.A., Hurben, A.K., Chao, C., et al.Small molecule inhibitors of TET dioxygenases: Bobcat339 activity is mediated by contaminating copper(II)ACS Med. Chem. Lett.13(5)792-798(2022)