TABLE 5.
Reversal of metabolism reprogramming by targeting epigenetics.
| Inhibitors | Target enzyme | Pharmacological agents | Mechanism | Indication | References |
|---|---|---|---|---|---|
| DNMT inhibitor | DNA methyltransferases | Azacitidine (approved) | Non-selective inactivating DNMT1, DNMT3A, and DNMT3B; Reversing the hypermethylation status in IDH1-mutant glioma cells | MDS, AML | Borodovsky et al. (2013); Turcan et al. (2013) |
| Decitabine (approved) | |||||
| Guadecitabine (phase-III) | |||||
| KDM inhibitor | LSD1 (Lysine demethylase) | ORY-1001 (phase-I) | Inhibiting histone demethylation | AML, SCLC, MDS | NCT02913443 |
| GSK2879552 (phase-I) | NCT02177812 | ||||
| NCT02034123 | |||||
| HDAC inhibitor | Histone deacetylases | Romidepsin (approved) | Prompting histone acetylation; Reducing glucose uptake, glycolytic flux, and lactate metabolism | T-cell Lymphoma, MM | Wardell et al. (2009); Alcarraz-Vizán et al. (2010); Amoêdo et al. (2011); Rodrigues et al. (2015) |
| Vorinostat (approved) | |||||
| Panobinstat (approved) | |||||
| Belinostat (approved) | |||||
| SIRT activator and inhibitor | SIRT6 (Histone deacetylases) | Linoleic acid | Activating or inhibiting histone deacetylation; Free fatty acid activates SIRT6 that inhibits glycolysis | Unknown | Feldman et al. (2013) |
| Myristic acid | |||||
| Oleic acid | |||||
| miRNA modulator | miRNAs | miRNA mimics | miRNA reversed silenced miRNA function; miRNA-143 could inhibit glycolysis by targeting hexokinase-II 3′-UTR; Anti-miRNA-21 could restore PTEN expression | Unknown | Meng et al. (2007); Gregersen et al. (2012) |
| miRNA sponges | |||||
| antisense oligonucleotides |
DNMT, DNA, methyltransferase; KDM, lysine demethylase; HDAC, histone deacetylase; SIRT, sirtuin; miRNA, microRNA; MDS, myelodysplastic syndrome; AML, acute myeloid leukemia; SCLC, small cell lung cancer; MM, multiple myeloma; 3′-UTR, 3′-untranslated region.