P1, N=24, Suspended, University of Utah | Recruiting --> Suspended

P1, N=18, Terminated, Epizyme, Inc. | Recruiting --> Terminated; Ipsen decided to discontinue all active tazemetostat clinical trials.

Virtual screening and molecular dynamics simulations identified acetyldigitoxin (ADT) as a potent EZH2 inhibitor, demonstrating superior binding affinity (-10.90 kcal/mol) and complex stability compared to the known inhibitor GSK126...ADT induced G0/G1 cell cycle arrest and promoted apoptosis, accompanied by upregulation of pro-apoptotic genes (Bax, Caspase-3) and downregulation of anti-apoptotic (Bcl-2) and cell cycle (CyclinD1) genes. Our integrated findings position ADT as a repurposed drug candidate for targeting EZH2 in NSCLC, warranting further preclinical investigation including direct enzyme inhibition assays.

P1, N=3, Terminated, Weill Medical College of Cornell University | N=38 --> 3 | Trial completion date: Dec 2028 --> Feb 2026 | Recruiting --> Terminated | Trial primary completion date: Dec 2026 --> Feb 2026; Low accrual

P2, N=23, Active, not recruiting, Weill Medical College of Cornell University | Recruiting --> Active, not recruiting | N=50 --> 23

P1/2, N=165, Not yet recruiting, Dizal Pharmaceuticals

P1/2, N=86, Not yet recruiting, Ruijin Hospital

Despite progress in understanding ES biology, treatment options are limited, and prognosis remains poor. Further studies are needed, but the rarity of the disease limits opportunities for conducting dedicated clinical trials or broader molecular characterization.

The study developed EIP103 as a first-in-class peptide degrader that targets EZH2 through multivalent, high-affinity interactions and induces conformational destabilization, representing a mechanism distinct from that of the small molecule inhibitor EPZ-6438...Additionally, molecular dynamics (MD) simulations and biochemical assays revealed that the peptide EIP103 binds to the SET domain of EZH2, altering its structure and triggering proteasomal degradation via Praja Ring Finger Ubiquitin Ligase 2 (PJA2)-mediated ubiquitination. Harboring both enzymatic inhibition and post-translational regulation properties, EIP103 exerts durable efficacy and activates antitumor immunity, making it a promising therapeutic candidate for TNBC.

P2, N=25, Recruiting, Fudan University | Trial primary completion date: Feb 2026 --> Feb 2027

An 80-year-old woman with relapsed nodal T-follicular helper cell lymphoma, not otherwise specified, developed severe watery diarrhea during valemetostat therapy...To the best of our knowledge, this is the first reported case of enhancer of zeste homolog 1 and 2 (EZH1/2) inhibitor-induced colitis. EZH1/2 inhibition may lead to T cell-mediated intestinal injury through epigenetic dysregulation; therefore, patients receiving EZH1/2 inhibitors who develop persistent diarrhea should undergo early endoscopic and histological evaluations.

P1, N=4, Not yet recruiting, Daiichi Sankyo Inc.