Discovery and comparative analysis of BBB-permeable EZH2 inhibitors for glioblastoma: A computational approach

Glioblastoma multiforme (GBM) is one of the most aggressive and lethal brain tumors with a 5-year survival rate of GBM is 5.5%. Enhancer of Zeste Homolog 2 (EZH2) was found to be one of the most promising therapeutic targets in GBM, a histone methyltransferase that mainly mediates gene silencing. A majority of EZH2 inhibitors, however, have poor blood-brain barrier (BBB) permeability thereby serving as ineffective inhibitors in CNS malignancies. The study summarises computational methods to contrast well established EZH2 inhibitors (Tazemetostat and EI1) with three additional, hitherto unknown but structurally related ones identified through SwissSimilarity searching, Losmapimod, Paquinimod, and Piboserod.