tazemetostat

Tazemetostat (EPZ6438) is a histone methyltransferase EZH2 inhibitor (IC50=11 nM) that is orally active, selective, and SAM-competitive. Tazemetostat exhibits antitumor activity and may be used for the treatment of epithelioid sarcoma follicular lymphoma.

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).

Tazemetostat trihydrochloride is a selective and orally available inhibitor of EZH2 (IC50: 4 nM for rat EZH2). It inhibits the activity of human PRC2-containing wild-type EZH2 (Ki: 2.5 nM). It inhibits EZH2 (IC50s: 11 and 16 nM in peptide assay and nucleo

Tazemetostat HCl is a potent, selective, and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity. EPZ-6438 induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells. Treatment of xenograft-bearing mice with EPZ-6438 leads to dose-dependent regression of MRTs with correlative diminution of intratumoral trimethylation levels of lysine 27 on histone H3, and prevention of tumor regrowth after dosing cessation. These data demonstrate the dependency of SMARCB1 mutant MRTs on EZH2 enzymatic activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers.

Tazemetostat de(methylene morpholine)-O-C3-O-C-COOH (Compound 21b), an EZH2 degrader, is utilized in lymphoma research [1].

Tazemetostat de(methyl morpholine)-COOH (compound 7), a PROTAC ligand for EZH2, enables the synthesis of PROTACs targeting this enzyme and exhibits potent inhibition of cell viability in diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes [1].

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.

S 2720 is a human immunodeficiency virus type 1 (HIV-1)-specific reverse transcriptase (RT) inhibitor quinoxaline.