Table 1 Selected small molecules with potential for clinical translation in CRC
From: Metabolic reprogramming in colorectal cancer: regulatory networks and therapy
Pathway | Target | Representative drugs | Comments | Most advanced clinical phase | Trial ID |
|---|---|---|---|---|---|
Glycolysis | GLUT1 | BAY-876 | Inhibitor | Preclinical | NA |
STF-31 | Inhibitor | Preclinical | NA | ||
HK | 2-Deoxy-D-glucose | Competitive HK1 inhibitor | Preclinical | NA | |
Lonidamine | HK2 inhibitor | Preclinical | NA | ||
3BP | HK2 inhibitor | Preclinical | NA | ||
PFKFB3 | PFK-158 | Inhibitor | Phase 1 | NCT02044861 | |
PKM2 | Shikonin | Inhibitor | Preclinical | NA | |
TEPP-46 | Activator | Preclinical | NA | ||
LDHA | GNE-140 | Inhibitor | Preclinical | NA | |
TCA cycle | PDH | CPI-613 | PDK activator | Phase 1&2 | NCT01832857 NCT02232152 NCT02232152 |
DCA | PDK2 inhibitor | Phase 1 | NCT00566410 | ||
Vitamin C | PDK1 inhibitor | Phase 1&2 | NCT04035096 | ||
IDH | AG-221 | IDH2 inhibitor | Phase 1&2 | NCT02273739 | |
AG-120 | IDH1 inhibitor | Phase 2 | NCT04056910 | ||
Pentose phosphate pathway | G6PD | RRx-001 | Inhibitor | Phase 2 | NCT02096354 |
| Â | G6PDi-1 | Inhibitor | Preclinical | NA | |
ME | NPD389 | ME2 Inhibitor | Preclinical | NA | |
Glutamate and Glutamine metabolism | GLS | CB-839 | Allosteric inhibitor | Phase 1&2 | NCT02861300 NCT03965845 NCT03263429 |
GPT | Aminooxyacetate | Pan-aminotransferase inhibitor | Preclinical | NA | |
ASCT2 | V-9302 | Aantagonist of glutamine transporter | Preclinical | NA | |
xCT | Sulfasalazine | Ferroptosis inducer | Phase 3 | NCT01198145 | |
SGOC metabolism | PHGDH | NCT-503 | Non-competitive inhibitor | Preclinical | NA |
SHMT | SHIN1 | Dual SHMT 1/2 inhibitor | Preclinical | NA | |
MTHFD2 | LY345899 | Folate analogue | Preclinical | NA | |
Tryptophan metabolism | IDO1 | 1-L-MT | Competitive inhibitor | Phase 1 | NCT05469490 NCT00739609 |
Epacadostat | Specifical inhibitor | Phase 1&2 | NCT02178722 NCT03361228 NCT02327078 NCT03516708 NCT03182894 | ||
TDO | HTI-1090 | Dual IDO1/TDO inhibitor | Phase 1 | NCT03208959 | |
AhR | BAY2416964 | AHR antagonist | Phase 1 | NCT04069026 NCT04999202 | |
IK-175 | AHR antagonist | Phase 1 | NCT04200963 | ||
Fatty acid metabolism | ACLY | NDI-091143 | Inhibitor | Preclinical | NA |
ACC | Soraphen A | Inhibitor | Preclinical | NA | |
FASN | TVB-2640 | Inhibitor | Phase 1 | NCT02980029 | |
ACSL | Triacsin C | PUFA analog | Preclinical | NA | |
SCD1 | A939572 | Inhibitor | Preclinical | NA | |
Cholesterol metabolism | CPT1 | Perhexiline | Inhibitor | Preclinical | NA |
SREBPs | Fatostatin | SREBP activity inhibitor | Preclinical | NA | |
ACAT1 | CI-976 | Competitive inhibitor | Preclinical | NA | |
HMGCR | Simvastatin | Competitive inhibitor | Phase 2&3 | NCT00994903 NCT02161822 NCT01238094 NCT02026583 NCT01110785 NCT00313859 | |
Rosuvastatin | Competitive inhibitor | Phase 1&2&3 | NCT02569645 NCT01011478 NCT05368805 | ||
LXR | LXR623 | LXR agonist | Preclinical | NA | |
GW3965 | LXR agonist | Preclinical | NA | ||
Nucleotide metabolism | DHODH | Leflunomide | Inhibitor | Phase 1 | NCT04997993 |
TS | 5-fluorouracil | TS inhibitor | Phase 1&2&3&4 | NCT02582970 NCT00932438 NCT00046995 |