Here, we report the effects on GBM, including primary GBM cell cultures, of two novel EZH2 inhibitors, MC4040 and MC4041, containing a N-phenylpyrrole core decorated with a cyclic amine (morpholine, MC4040, or piperidine, MC4041), often present in known EZH2i, and carrying the 2-pyridone moiety known to be crucial for the EZH2 inhibiting activity [51]. The gene discussed is EZH2; the disease is glioblastoma.