Cover Feature: Development of Novel Inhibitors for Histone Methyltransferase SET7/9 based on Cyproheptadine (ChemMedChem 15/2018)

The Cover Feature shows the inhibitor of histone methyltransferase SET7/9 based on a novel scaffold, cyproheptadine, which is used clinically as a serotonin receptor antagonist or histamine receptor antagonist. Among its derivatives, a compound bearing a 2‐hydroxy group showed the most potent activity, while a 3‐hydroxy group or other hydrophilic functional groups such as acetamide decreased the activity. Structural analysis clarified a rationale for the improved potency only by tightly restricted location and type of hydrophilic group. These results are helpful for further structure‐based development of SET7/9 inhibitors. More information can be found in the Full Paper by Tomoya Hirano et al. on page 1530 in Issue 15, 2018 (DOI: 10.1002/cmdc.201800233).