Table 5.
The effect of select histone methyltransferase and histone demethylase inhibitors in GBM pathophysiology.
| Treatment/Drug | Target | Effect | Cell model(s) used | References |
|---|---|---|---|---|
| Tranylcypromine | KDM1A | Increased cell death in combination with vorinostat | LN-18, U87 | (106) |
| NCL-1 & NCD-38 | KDM1A | Reduced viability and increased survival | GSCs, U251, murine mouse model | (105) |
| GSK-14 | KDM class/KDM2B | Decreased cell viability | GSCs | (111) |
| SD70 | KDM4C | Decreased cell viability | U251, U87 | (117) |
| JIB-04 | KDM class/KDM5A | Activated autophagy and apoptosis | A172, U251, GSCs | (118, 120) |
| GSKJ4 | KDM6B | Decreased cell growth and increased apoptosis | U251, GSCs | (36, 120) |
| DMOG | KDMs 2-7 | Induced DNA damage and apoptosis | GSCs | (116) |
| AC1Q3QWB | EZH2 | Increased cell death and decreases tumor growth when combined with DZNep | N5, N33, murine flank model | (184) |
| DZNep | EZH2 | Decreased self-renewal and tumor growth | U87, U251, LN229, D54, GSCs, murine mouse models | (12, 19, 131, 132, 181, 190) |
| GSK126 | EZH2 | Decreased pSTAT3 | GSCs | (19) |
| PCI-24781 | EZH2 | Reduced proliferation and induced cell cycle arrest and apoptosis | LN18, LN229, U87 | (137) |
| UNC1999 | EZH2 | Decrease cell viability, induced autophagy, reduce flank tumor growth | GSCs, murine mouse model | (179) |
| EPZ6438 | EZH2 | Increased apoptosis and survival | GSCs, murine mouse model | (135, 181) |
| MC4040 & MC4041 | EZH2 | Cell cycle arrest, decreased invasiveness | U87, patient derived cell cultures | (139) |
| BIX01294 | EHMT2 | Decreased self-renewal and cell viability, activation of autophagy, reduced tumor growth | U87, U251, LN18, LN229, D54, GSCs, murine mouse model | (148, 150, 151, 187, 190, 191) |
| Chaetocin | SUV39H1 | Reduced proliferation and clongenic ability | T98G | (156) |
| SGC707 | PRMT3 | Inhibited cell growth and glycolysis, Inhibited tumor growth | U87, U251, patient derived GSCs, nude mouse flank model | (163) |
| HLCL65, CMP12 | PRMT5 | Increased cell death, improved survival | Patient derived cell cultures, zebrafish GBM model | (165) |
| CMP5 | PRMT5 | Inhibits self-renewal and cell cycle progression, increased apoptosis and survival, long term survivors | Patient derived cell cultures, zebrafish GBM model | (165) |
| GSK591 & LLY-283 | PRMT5 | Inhibits proliferation and sphere formation, increases apoptosis and survival, crosses BBB | GSCs, murine mouse model | (167) |
| EPZ020411 | PRMT6 | Induces cell cycle arrest, decreases sphere formation, increased survival | GSCs, murine mouse model | (162) |
A summary of the impact of select histone methyltransferase and histone demethylase inhibitors on GBM pathophysiology, and the corresponding model system(s) used and reference to the original publication(s).