Table 2 An overview of EZH2 inhibitors based on pre-clinical and clinical studies

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]