The nanomolar enzymatic inhibitory potency of DNMT1 of both 7-aminoalkoxy-quinazolines 12 and 13 is about ten times that of the positive control SAH. Despite the high variability across DNMT inhibitory assays and the challenge to reproduce the IC 50 values accurately across different laboratories, there are few compounds reported in the literature with low nanomolar inhibition of DNMT1. For instance, in one of the most recent studies testing different DNMTi under the same assay conditions, 5 (GSK3685032) strongly inhibited DNMT1 (IC 50 = 30 nM) and did not inhibit DNMT3A and 3B (Figure ). In that work, Pappalardi et al., also tested the well-known pan inhibitor 3 (SGI-1027), showing IC 50 values of 1,030 nM (DNMT1); 13,000 nM (DNMT3A), and 7,000 nM (DNMT3B). In the work of Pappalardi et al., SAH (also used as a reference) had IC 50 values of 540 nM, 100 nM, and 90 nM for DNMT1, DNMT3A, and DNMT3B, respectively. Such values for the positive control generally agree with the IC 50 values measured under the assay conditions used in this work (340 nM, 100 nM, and 30 nM for DNMT1, DNMT3A, and DNMT3B, respectively, Table in the Supporting Information).