Figure 4.

(A) Detailed interactions of 10 with Dot1L (pdb 6TEL). Amino acid side chains engaging in key interactions with the ligand are illustrated as sticks, polar contacts are highlighted as dotted red lines. Compared to 3, the piperazine triazine moiety of 10 increases the stacking contacts with Phe243 and Phe129-Pro130 and the hydrophobic pocket of the benzhydrylamino moiety is filled more efficiently. (B) Detailed interactions of 11 with Dot1L (pdb 6TEN). Amino acid side chains engaging in key interactions with the ligand are illustrated as sticks, and polar contacts are highlighted as dotted red lines. Compared to 10, the amino methoxy triazine moiety of 11 makes efficient stacking contacts with Phe243 and Phe129-Pro130 and the reintroduction of the sulfonamide as hydrogen bond donor shortens the ligand distance with Ser269 and Ser311 carbonyl groups.