Recently,the EZH2 catalytic inhibitor tazemetostat hit the market after FDAapproval for locally advanced epithelioid sarcoma and follicular lymphoma.48−50 However, the work for medicinal chemists is not finished yet asorthosteric EZH2 inhibitors induce resistance despite being alreadyselective toward many other methyltransferases. The gene discussed is EZH2; the disease is epithelioid sarcoma.