Table II.
Inhibitors of PHGDH.
| Inhibitor name | Inhibitor type | Inhibition mechanism |
|---|---|---|
| Indole derivative 1 | Orthosteric inhibitors | Competitive inhibitors. Bind with the NAD+ pocket of PHGDH, and inhibit its activity |
| Compound 9 (CBR-5884) | Allosteric inhibitors | Noncompetitive inhibitors. Bind to a Cys in the non-active site and disrupts its oligomeric state |
| (DSF) | Allosteric inhibitors | Noncompetitive inhibitors. Convert PHGDH tetramer into either an inactive dimer to inhibit PHGDH activity |
| Compound 14 (NCT-503) | Allosteric inhibitors | Noncompetitive inhibitors. Closely bind to the active site as a mutation of C234 in the protein's active site to reduce the inhibitory effect of PHGDH |
| α-ketothioamide derivatives. | Allosteric inhibitors | Decrease PHGDH activity and selectively strain the proliferation of cancer cells with elevated PHGDH expression |
| PKUMDL-WQ-2101 | Non-NAD+ competing allosteric inhibitors | Form hydrogen-bond networks with R134, K57 and T59 of site I to inhibit PHGDH activity |
| PKUMDL-WQ-2201 | Non-NAD+ competing allosteric inhibitors | Form hydrogen-bond networks with T59, T56 and K57 of site II to inhibit PHGDH activity |
| Azacoccone E | Natural compounds, allosteric inhibitors | Noncompetitive inhibitors. Fit at the allosteric site of PHGDH to diminish enzyme activity. |
| Iox A | Allosteric inhibitors | Directly coordinate at the allosteric site in the back side of the active site of PHGDH |
DSF, disulfiram; Iox A, Ixocarpalactone A; PHGDH, phosphoglycerate dehydrogenase.