Table 1.
Cancer drugs targeting metabolic pathways that are approved, or under investigation in clinical trials.
| Metabolic Pathway | Target | Drug |
|---|---|---|
| Glycolysis | GLUT1 | WZB117, BAY-876 |
| Hexokinase | 2-Deoxyglucose | |
| Pyruvate Kinase M2 (PKM2) | TEPP-46 | |
| Lactate dehydrogenase A (LDHA) | Quinoline, 3-sulfonamides, FX11, PSTMB | |
| Monocarboxylate transporter 1 (MCT1) | AZD3965 | |
| Amino acid metabolism | Glutaminase 1 (GLS1) | CB-839, IPN60090 |
| ASCT2 (SLC1A5) | GPNA | |
| Multiple targets | JHU-083, DRP-104 | |
| Phosphoglycerate dehydrogenase (PHGDH) | CBR-5884, NCT-503 | |
| Indoleamine-2,3-dioxygenase-1 (IDO1) | Epacadostat, indoximod | |
| Circulating asparagine | L-Asparaginase | |
| Large neutral amino acid transporter (LAT1) | JPH203 | |
| Mitochondrial metabolism | Pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase | CPI-613 |
| Electron transport chain complex 1 | Metformin, IACS-010759, IM156 | |
| Lipid metabolism | ATP-citrate lyase (ACLY) | SB-204990 |
| Acetyl-CoA carboxylase (ACC) | Soraphen-A | |
| fatty acid synthase (FASN) | TVB-2640 | |
| Enzymes mutated in cancer | Mutant isocitrate dehydrogenase 1 (IDH1) | Ivosidenib, IDH305, BAY1436032, LY3410738, FT-2102 |
| Mutant isocitrate dehydrogenase 2 (IDH2) | Enasidenib | |
| Nucleic acid synthesis | Thymidylate synthase (TS) | 5-Fluorouracil, capecitabine, pemetrexed, raltitrexed |
| Dihydrofolate reductase (DHFR) | Methotrexate, pemetrexed | |
| Glycinamide ribonucleotide formyltransferase (GARFT) | Pemetrexed | |
| Dihydroorotate dehydrogenase (DHODH) | Brequinar, leflunomide | |
| Ribonucleotide reductase (RNR) | Gemcitabine, clofarabine, fludarabine, cladribine, cytarabine | |
| 5-Phosphoribosyl-1-pyro-phosphatase (PRPP) amidotransferase | Mercaptopurine, thioguanine |