Extensive studies on the pharmacokinetics of EZH2 inhibitors allowed to identify a selection of molecules, with better bioavailability and higher specificity that minimize off-target effects, directed to the conserved Set-domain of EZH2 that exhibit methyltransferase activity and has been identified as a mutated catalytic domain in human cancers, with more than 50 mutations reported. Here, EZH2 is linked to cancer.