Table 1.
Key enzymes/transporters or genes that may participate in the regulation of ferroptosis in amino acid metabolism
| Compound/Drug | Target | Mechanism | Phase (status) | Reference |
|---|---|---|---|---|
| sorafenib | system Xc- | Prevents cystine import, causes GSH depletion | Approval | 123 |
| erastin | system Xc- | Prevents cystine import, causes GSH depletion | Phase I | 1 |
| sulfasalazine | system Xc- | Prevents cystine import, causes GSH depletion | Approval | 1 |
| BSO | GCL | Inhibits GCL, inhibits GSH synthesis. | Phase I | 124 |
| artesunate | glutathione S-transferase | Inhibits glutathione S-transferase, causes GSH depletion | Approval | 125 |
| cyst(e)inase | Cyst(e)ine | Induces cyst(e)ine depletion | 32 | |
| CB-839, BPTES 968 |
GLS | Inhibits the conversion of Gln to Glu | Phase I/II | 87, 91 |
| AOA | GOT1 | Inhibits the conversion of Glu to a-KG |
87 | |
| ADI-PEG20 | Arginine | degrades and consumes Arg | Phase III | 126 |
| CB-1158 | Arginase | Inhibiting arginase | Phase II | 127 |
| GPNA, Tamoxifen Raloxifene |
ASCT2 | Inhibits glutamine uptake | 91, 128 | |
| Gene | Protein | Mechanism | Phase (status) | Reference |
| CDO1 | cysteine dioxygenase | enzyme that catalyzes the conversion of cysteine to taurine and reduces GSH synthesis | 53 | |
| CISD1 | CDGSH iron-sulfur domain 1 | Inhibits mitochondrial iron transport into the matrix | 129 | |
| SLC7A11 | Solute carrier family 7 member A11, xCT | a component of system Xc-, requires for cystine import | 82 | |
| CARS | cysteinyl-tRNA synthetase | knockdown causes increased transsulfuration pathway activity, and resistance to ferroptosis | 58 | |
| NFS1 | cysteine desulfurase | enzyme involves in synthesizing iron-sulfur clusters using sulfur from cysteine |
64 | |
| SLC1A5 | solute carrier family 1 member 5 |
amino acid transporter feeding glutaminolysis | 86 | |
| GCLC | glutamate-cysteine ligase catalytic subunit |
enzyme involves in GSH synthesis |
124 | |
| BCAT2 | branched-chain amino acid transaminase-2 | activation could antagonize system Xc- inhibition and protect from ferroptosis. | 104 | |
| I3P | indole-3-pyruvate | scavenges free radicals and activates anti-oxidative stress pathways | 110 | |
| LO | L-lysine α-oxidase | enzyme catalyzes the oxidative deamination of L-lysine to activate ferroptosis | 122 |