Table 4.
Histone methyltransferases and demethylases with reported functions and representative methyltransferase/demethylase inhibitors in lung cancer (including NSCLC)
| Enzymes and their inhibitors | Target | Function | Reference |
|---|---|---|---|
| Histone methyltransferases | |||
| MLL2 | H3K4 | Loss of expression and deleterious mutations in NSCLC | [145] |
| SMYD2 | H3K36 | Contributed to NSCLC cell growth | [148] |
| SETD2 | H3K36 | Deleterious mutations in primary NSCLC | [149] |
| DOT1L | H3K79 | Contributed to NSCLC cell growth | [167] |
| PRMTs | Arginine on H3 and H4 | Contributed to NSCLC cell growth and overexpressed in TKI-resistant NSCLC | [164] |
| Histone demethylases | |||
| KDM2A | H3K36me2/me1 | Overexpressed in NSCLC | [157] |
| PAD4 | Arginine on H3 and H4 | Overexpression led to gefitinib resistance in NSCLC | [164] |
| KDM3 | H3K9me2/me1 | Overexpressed in NSCLC | [159] |
| EZH2 inhibitors | |||
| Clinical Trial Number | |||
| DZNep | SAH hydrolase inhibitor (Ki = 50 pM) | NA | [168] |
| GSK2816126 (GSK126) | SAM-competitive EZH2 inhibitor (IC50 = 9.9 nM | NCT02082977 | [169] |
| EPZ6438 (Tazemetostat) | SAM-competitive EZH2 inhibitor (Ki = 2.5 nM) (IC50 = 11 nM) | NCT01897571 NCT02601950 NCT02601937 | [170] |
| CPI1205 | SAM-competitive EZH2 inhibitor | NCT02395601 | [171] |
| LSD1 inhibitor | |||
| RG6016 (ORY-1001) | FAD-dependent irreversible LSD1 inhibitor (IC50 b 20 nM) | NCT02913443 | [172] |