Table 9.
Major peptide PROTACs and their biological impacts
| Name | Target | Target ligand | E3 ligase | E3 ligase ligand | Biological impacts |
|---|---|---|---|---|---|
| Api-PROTAC | AHR | Apigenin | CRL2 (VHL) | A pentapeptide sequence derived from HIF1α | Potential roles against AHR positive disorders332,333 |
| Tri_a-PROTAC | AKT | PCC | CRL2 (VHL) | A heptapeptide derived from HIF1α | Potential roles against AKT positive disorders227 |
| PROTAC-3 | AR | DHT | CRL1 (β-TRCP) | A phosphopeptide derived from IκBα | Potential roles against AR positive disorders228 |
| PROTAC-5 | AR | DHT | CRL2 (VHL) | A heptapeptide derived from HIF1α | Potential roles against AR positive disorders202 |
| PROTAC-2 | ER | Estradiol | CRL1 (β-TRCP) | A phosphopeptide derived from IκBα | Potential roles against ER positive disorders228 |
| E2-SMPI | ER | Estradiol | CRL2 (VHL) | An octapeptide or pentapeptide derived from HIF1α | Inhibition of endothelial cell differentiation220–222 |
| PROTAC-4 | FKBP12 | AP21998 | CRL2 (VHL) | A heptapeptide derived from HIF1α | Potential roles against FKBP12 positive disorders202 |
| phosphoPROTAC-1 | FRS2α | Tyrosine phosphorylation sequences of TrkA | CRL2 (VHL) | A heptapeptide derived from HIF1α | Inhibition of neuronal differentiation223 |
| HBx-PROTAC | HBx | The oligomerization domain of HBx | CRL2 (VHL) | ODD domain of HIF1α | Potential roles against HBV infection and development of liver cancer225 |
| Fu-SMPI | MetAP-2 | Fumagillol | CRL2 (VHL) | An octapeptide derived from HIF1α | Potential roles against MetAP-2 positive disorders220 |
| phosphoPROTAC-2 | PI3K | Tyrosine phosphorylation sequences of ErbB3 | CRL2 (VHL) | A heptapeptide derived from HIF1α | Loss of viability of breast cancer cells223 |
| Smad3-PROTAC | Smad3 | SMC | CRL2 (VHL) | A pentapeptide derived from HIF1α | Potential roles against the development of renal fibrosis226 |
| TH006 | Tau | Sequences derived from β-tubulin | CRL2 (VHL) | A heptapeptide derived from HIF1α | Reduced proteotoxic effects among AD mice224 |
Abbreviations: NS: not specific; AHR: aryl hydrocarbon receptor; PCC: protein-catalyzed capture agent; DHT: dihydroxytestosterone; FRS2α: fibroblast growth factor receptor substrate 2 α; TrkA: tropomyosin receptor kinase A; PI3K: phosphatidylinositol-3-kinase; ErbB3: erythroblastosis oncogene B3; MetAP-2: methionine aminopeptidase-2; SMC: small molecule compound; ERK: extracellular regulated protein kinase; ODD: oxygen-dependent degradation; E2-SMPI: Estradiol-Small molecule proteolysis inducer; SNIPER: specific and nongenetic IAPs-dependent protein erasers; AR: androgen receptor; ER: estrogen receptor; AD: Alzheimer’s Disease.