Table 1.
Current and potential therapeutic targets based on non-canonical metabolic roles.
| Target | Agent | Mechanism to Target | References |
|---|---|---|---|
| Glutaminase 1 | CB-839 | NCT02071927 | |
| NCT02071888 | |||
| NCT02071862 | |||
| GRM1 | Riluzole | Pro-tumorigenic glutamate signaling. | NCT00903214 |
| NCT01018836 | |||
| NCT01303341 | |||
| NCT00866840 | |||
| HDAC | Belinostat | Catalytic activity resulting in hypoacetylation. | NCT00993642 |
| Panobinostat | NCT01075308 | ||
| Vorinostat | NCT02635061 | ||
| SB939 | NCT01528501 | ||
| ACY-241 | NCT00274651 | ||
| mIDH | AG-221 | Production of on co metabolite 2-hydroxyglutarate. | NCT01915498 |
| AG-120 | NCT02073994 | ||
| AG-881 | NCT02492737 | ||
| IDH305 | NCT02987010 | ||
| Methyltransferase | 5-azacytidine, 5-aza-2’-deoxycytidine | Catalytic activity resulting in hypermethylation. | NCT03019003 |
| NCT03182894 | |||
| NCT02159820 | |||
| NCT00084981 | |||
| ACLY | 2,2-difluorocitrate Sulfoximine | Catalytic activity producing Acetyl-CoA which induces hyperacetylation. | [109,110] |
| AMF | ERI4P G6P |
Pro-metastatic, autocrine and paracrine signaling via gp78. | [111] |
| SLC1A5 (ASCT2) | AABA Benzylserine Benzylcysteine GPNA |
Import of glutamine, which is an important carbon source for a number of pro-metastatic processes. | [112,55,56,54] |
| SLC7A11 (xCT) | Sulfasalazine Erastin Sorafenib |
Release of glutamate which can act as a pro-metastatic signaling molecule. | [113–115] |
| AMPAR | GYKI-52466 CFM-2 |
Glutamate signaling which can drive metastasis. | [116] |
| HAT | C646 PU139 PU141 |
Increased activity resulting in hyperacetylation. | [117,118] |
| SPLA2 | Varespladib PLIs |
Secretion and binding to receptors that drive Wnt signaling. | [119,120] |
| GAPDH (Potential) | N/A | GAPDH binding to EMT transcription factor sp1 | |
| PKM2 (Potential) | N/A | PKM2 binding to HDAC3 and TGIF2. | |
| PRDX4 (Potential) | N/A | Secretion and function as an osteoclastogenic signaling factor. |