However, the generation of stable interactions with ASP 583, ASP 588, CYS 1288, and GLN 1289 (Figure -A1 and 3-A2). Interestingly, 13 has been distinguished by other key interactions (GLU 766, VAL 1330, ASN 1332, and PHE 1336). Despite the differences in key interactions, the compounds studied tend to establish the conformation (reducing the RMSD values) of CXXC (647 -691 aa) and autoinhibition (699 -733 aa) domains of DNMT1 (Figure -A3, 3-B3), in relationship with SAM (Figure -C in the Supporting Information). We emphasize that these domains are present only in DNMT1 and are not its 3A or 3B isoforms, which could explain the selective enzymatic inactivation of DNMT1. Additionally, we analyze the specific conformational changes associated with the interaction of 12 and 13 against DNMT1 (Figure in the Supporting Information). Recently, we described at the structural level the conformational changes generated on G9a in their SET domain by the interaction with quinoline-based compounds. This work describes the conformational changes associated with the interaction of quinoline-based compounds against the CXXC and autoinhibition domain on DNMT1.