Table 2.
PROTACs in melanoma preclinical models and in clinical trials
| Target | PROTAC | E3 Ligase | Ligand | Reference | Research status | |
|---|---|---|---|---|---|---|
| BRAF | Compound-2 | CRBN | Rigosertib | 97 | In vitro | |
| P4B | CRBN | BI882370 | 32 | In vivo | ||
| P5B | CRBN | 99 | In vitro | |||
| Compound-12 | CRBN | Vemurafenib | 98 | In vitro | ||
| Compound-23 | CRBN | 98 | In vitro | |||
| Compound-24 | CRBN | PLX-8394 | 101 | In vitro | ||
| CST905 | VHL | 104 | In vitro | |||
| SJF-0628 | VHL | Vemurafenib | 102 | In vivo | ||
| CFT1946 | CRBN | 93 | Phase I trial (NCT05668585*) | |||
| BAF | SMARCA2/4 | ACBI1 | VHL | Class VIII bromodomain-ligand | 111 | In vitro |
| BRD9 | CFT8634 | CRBN | BRD7/9-ligand | 110, 111 | Phase I/II trial (NCT05355753*) | |
| FHD609 | CRBN | 110, 111 | Phase I/II trial (NCT04965753*) | |||
| BRD4 | RNK05047 | HSP90 | BRD4-ligand | 116 | Phase I/II trial (NCT05487170*) | |
| ARV-825 | CRBN | 120–122 | In vivo | |||
| ARNIPL | CRBN | Palmitoyl-DL-carnitine chloride, ARV-825 | 118 | In vitro | ||
| LARPC | CRBN | 118 | In vitro | |||
| MZ1 | VHL | JQ1 | 128 | In vivo | ||
| NR4A1 | NR-V04 | VHL | Celastrol | 148 | In vivo | |
| MAGE-A3 | KL465 | VHL | MAGE-A3-ligand | 163 | In vitro | |
| MDM2 | MSDNc | MDM2 | MDM2-ligand | 170 | In vivo | |
| CD147 | Compound-6a | CRBN | Pseudolaric acid B | 191 | In vivo | |
| Bcl-xL | XZ739 | CRBN | Navitoclax | 197 | In vitro | |
| XZ424 | CRBN | A1155463 | 197 | In vitro | ||
| PZ15227 | CRBN | Navitoclax | 197 | In vivo | ||
| DT2216 | VHL | 11, 198, 199 | Phase I/II trial (NCT04886622*, NCT06620302*) | |||
| PZ703b | VHL | 197 | In vitro | |||
| 753b | VHL | 197 | In vitro | |||
| Compound-8a | IAP | 11 | In vitro | |||
| NAMPT | 632005 | CRBN | SIAIS630120 | 206 | In vivo | |
| pCREB | D16 | CRBN | Rhein | 209 | In vivo | |
| MITF | WZS0347 | CRBN | TT-012 | 215 | In vitro | |
| TYR | TYR degrader | VH032-Azi + Alk-Tln | 220 | In vivo | ||
| RPL15 | SN38 | CRBN | SN-38 | 222 | In vivo | |
| MEK1/2 | MS432 | VHL | 223 | In vitro | ||
| Folate-MS432 | VHL | MS432 | 225 | In vitro | ||
| MS928 | VHL | 224 | In vitro | |||
| MS934 | VHL | 224 | In vitro | |||
| MS910 | CRBN | 224 | In vitro | |||
| Compound-3 | MEK1/2-ligand | 226 | In vitro | |||
| Compound-4 | MEK1/2-ligand | 226 | In vitro | |||
| Compound-5 | MEK1/2-ligand | 226 | In vitro | |||
| CDK4/6 | NGP-28 | CRBN | Ribociclib | 232 | In vivo | |
| PD-L1 | BMS-37-C3 | CRBN | BMS-37 | 243 | In vitro | |
*NCT05668585, BRAF V600 mutant solid tumors; NCT05355753, locally advanced or metastatic SMARCB1-perturbed cancers; NCT04965753, advanced SMARCB1-loss tumors; NCT05487170, subjects with advanced solid tumors/diffuse large B-cell lymphoma; NCT04886622, relapsed/refractory malignancies; NCT06620302, relapsed or refractory solid tumors [3]