ezh1/2

Tazemetostat hydrobromide (E-7438 hydrobromide) is a potent and selective EZH2 inhibitor. Tazemetostat hydrobromide inhibits the activity of human polycomb repressive complex 2 (PRC2)-containing wild-type EZH2 (Ki: 2.5 nM). Tazemetostat hydrobromide also inhibits EZH1 (IC50: 392 nM).

UNC1999 is a orally bioavailable, effective and specific inhibitor of EZH2 (IC50=2 nM) and EZH1 (IC50=45).

Valemetostat tosylate is a dual inhibitor of EZH1 2 and used in the research of relapsed refractory peripheral T-cell lymphoma.

Valemetostat (DS-3201) is an EZH1 2 inhibitor that can be used to study relapsed refractory peripheral T-cell lymphoma.

HH-2853 is a potent inhibitor targeting EZH1 2, demonstrating significant antitumor activity. Its IC50 values for both wild-type and mutant EZH2 range from 2.21-5.36 nM, comparable to tazemetostat. HH-2853 is more effective against EZH1, with an IC50 of 9.26 nM, notably lower than tazemetostat's 58.43 nM. However, at concentrations up to 10 μM, it exhibits minimal inhibitory activity on 36 types of histone-modifying enzymes. On the cellular level, HH-2853 effectively inhibits mono-, di-, and tri-methylation of H3K27 in various cancer cell lines with wild-type or mutant EZH2, without affecting other methylation types on histone H3 at concentrations up to 10 μM. Additionally, HH-2853 significantly reduces cell viability in multiple cancer cell lines carrying EZH2 GOF mutations or SWI SNF complex alterations, and demonstrates superior antitumor effects compared to tazemetostat in several tumor xenograft models at equivalent doses.

(R)-OR-S1 is a SAM-competitive, highly selective, orally bioavailable dual inhibitor of EZH1/2.