Successful strategies in the discovery of small-molecule epigenetic modulators with anticancer potential.

As a class, epigenetic enzymes have been identified as clear targets for cancer therapeutics based on their broad hyperactivity in solid and hematological malignancies. The search for effective inhibitors of histone writers and of histone erasers has been a focus of drug discovery efforts both in academic and pharmaceutical laboratories and has led to the identification of some promising leads. This review focuses on the discovery strategies and preclinical evaluation studies of a subset of the more advanced compounds that target histone writers or histone erasers. The specificity and anticancer potential of these small molecules is discussed within the context of their development pipeline.