In preclinical evaluations, PC14586 restored p53Y220C to wildtype conformation, induced p53-regulated gene expression such as p21 and MDM2, and regressed TP53Y220C mutant tumor in vivo.310 Remarkably, in an engineered mouse model carrying TP53Y220C mutation, PC14586 combined an anti-PD1 antibody led to 6 out of 10 complete response and dramatically extended median survival time.311 Recently, preliminary response was reported in patients harboring TP53Y220C mutation during PC14586 dose escalation.312 PC14586 reached maximal tolerated dose at 1500 mg BID with acceptable safety profile. The gene discussed is TP53; the disease is neoplasm.