Table 2.

An overview of EZH2 inhibitors based on pre-clinical and clinical studies

EZh2 inhibitor	In vitro/in vivo/clinical trial	Remarks	References
GSK2816126	Clinical trial (phase I)	Preventing the progression of solid tumors and lymphoma Exerting mild anti-tumor activity Low half-life restricts its anti-tumor activity Intravenous administration	[76]
GSK126	In vitro (DLBCL cell line) In vivo (xenografts)	Preventing methyltransferase activity of EZH2 Decreasing H2K27me3 levels Stimulating expression of PCR2 target genes	[74]
EED226	In vivo (human lymphoma xenograft tumors)	Triggering conformational changes in EED site of H3K27me3 Suppressing PRC2 activity Preventing tumor growth	[75]
GSK926 GSK343	In vitro (HCC1806 breast cancer cells)	Reducing nuclear H3K27me3 levels in a concentration-dependent manner Acting like other SAM compounds in suppressing EZH2 activity	[94]
EPZ-6438	In vitro (lymphoma cells) In vivo (EZH2-mutant NHL xenograft-bearing mice)	Acting in a time- and concentration-dependent manner Preventing lysine 27 methylation of H3K27me3 Suppressing EZH2 signaling Exerting anti-tumor activity	[95]
SAH-EZH2 (a peptide)	In vitro (MLL-AF9 leukemia cells)	Proliferation inhibition Inducing monocyte-macrophage differentiation Inhibiting EZH2 signaling by impairing EZH2-EED complex	[96]
AZD9291	In vitro (lymphoma and breast cancer cells)	Inhibiting PRC2 activity by disrupting EZH2-EED interaction Reducing EZH2 expression at mRNA and protein levels via miRNA-34a overexpression	[97]
Astemizole	In vitro (SU-DHL6, Toledo, DB, SU-DHL4, and Pfeiffer lymphoma cell lines)	Suppressing growth of cancer cells Inhibiting EZH2 signaling via preventing interaction between PRC2 and EZH2-EED complex	[98]
Wedelolactone	In vitro (HepG2, K562 and 293T cells)	Binding to EED and inhibiting EED and EZH2 interaction Mediating PRC2 degradation Suppressing cancer proliferation	[99]