Enhancer of zeste homolog 2 (EZH2) is a histone-lysine N-methyltransferase enzyme encoded by EZH2 gene. And it participates in histone methylation and, ultimately, transcriptional repression.
Meanwhile, mutation or over-expression of EZH2 has been linked to many forms of cancer including, but not limited to, breast, prostate, melanoma, and bladder cancer. Furthermore, EZH2 inhibits genes responsible for suppressing tumor development, and blocking EZH2 activity may slow tumor growth. EZH2 has been targeted for inhibition because it is upregulated in multiple cancers.
Valemetostat (DS-3201) is a First-in-class EZH1/2 Dual Inhibitor for Adult T-cell Leukemia Research
Valemetostat (DS-3201), a first-in-class EZH1/2 dual inhibitor with IC50 values ＜10 nM. And Valemetostat can be used for the research of relapsed/refractory peripheral T-cell lymphoma.
In Vitro, Valemetostat (1-1000 nM) strongly and specifically inhibits EZH1 and EZH2 with IC50 values ＜10 nM. Valemetostat (100 nM; 7 days) effectively removes H3K27me3 and also prevents unexpected gain of H3K27me3. Valemetostat (0.1-100 nM; 7 days) potently inhibits H3K27me3 by low-dose treatment in the sensitive lymphoma types. In Vivo, Valemetostat (0.01 mg/g; i.p.; once) prevents the changes of H3K27me3 after exercise training.
In conclusion, Valemetostat (DS-3201) is a First-in-class EZH1/2 Dual Inhibitor for Adult T-cell Leukemia Research.
Reference:
[1]. J Physiol. 2022 Jul;600(14):3331-3353.
[2]. Cell Rep. 2019 Nov 19;29(8):2321-2337.e7.