Table 1.
Examples of PROTAC targets being pursued therapeutically, their class, and the E3 ligase used in the PROTAC mode of action
| Target | Class | E3 ligase |
|---|---|---|
| BRD2/4/7/9 | Transcription factor | CRBN |
| VHL | ||
| MDM2 | ||
| RIPK2 | Kinase | VHL |
| Akt | Kinase | VHL |
| ABL | Kinase | VHL |
| BCR‐ABL | Fusion protein | CRBN |
| VHL | ||
| cIAP1 | ||
| Smad3 | Transcription factor | VHL |
| Tau | Scaffolding activity | VHL |
| Keap1 | ||
| DHODH | Enzyme | VHL |
| CDK6/9 | Kinase | CRBN |
| Sirt2 | Deacetylase | CRBN |
| BTK | Kinase | CRBN |
| MDM2 | ||
| ALK | Kinase | CRBN |
| VHL | ||
| HDAC6 | Deacetylase | CRBN |
| VHL | ||
| TRIM24 | E3 | VHL |
| EGFR | Kinase | VHL |
| CRBN | ||
| IRAK4 | Kinase | CRBN |
| VHL | ||
| STAT3 | Transcription factor | CRBN |
| MetAP‐2 | Enzyme | SCF |
| VHL | ||
| ER | Transcription factor | SCF |
| VHL | ||
| CRBN | ||
| cIAP1 | ||
| AR | Transcription factor | SCF |
| VHL | ||
| CRBN | ||
| MDM2 | ||
| cIAP1 | ||
| AHR | Transcription factor | VHL |
| CRABP | Transporter | cIAP1 |
| RAR | Transcription factor | cIAP1 |
| DAPK1 | Kinase | CMA |
| PSD‐95 | Kinase | CMA |
| α‐Synuclein | Scaffolding activity | CMA |
| TACC3 | Scaffolding activity | APC/C |
| IKZF1/3 | Transcription factors | CRBN |
| Bcl6 | Transcription factor | CRBN |
| FAK | Kinase | VHL |
| CRBN | ||
| MET | Kinase | VHL |
| Bcl‐2/Bcl‐Xl | Transcription factors | CRBN |
| VHL |
Table 1 . Examples of PROTAC targets being pursued therapeutically, their class and the E3 ligase used in the PROTAC mode of action. Met‐AP2 (methionine aminopeptidase 2); ER (estrogen receptor); AR (androgen receptor); CRABP (cellular retinoic acid‐binding protein); RAR (retinoic acid receptor); DAPK1 (death‐associated protein kinase 1); PSD‐95 (postsynaptic density protein 95); TACC3 (transforming acidic coiled‐coil‐containing protein 3); IKZF (ikaros family zinc finger protein); Bcl6 (b‐cell lymphoma 6); FAK (focal adhesion kinase); MET (proto‐Oncogene, Receptor Tyrosine Kinase); BRD (bromodomain‐containing protein); RIPK2 (receptor‐interacting serine/threonine‐protein kinase 2); Akt (protein kinase B); ABL (abelson murine leukemia); BCR‐ABL (breakpoint cluster region protein‐abelson murine leukemia); Smad3 (SMAD family member 3); DHODH (dihydroorotate dehydrogenase); CDK (cyclin dependent kinase); Sirt2 (sirtuin 2); BTK (bruton tyrosine kinase); ALK (ALK receptor tyrosine kinase); HDAC6 (histone deacetylase 6); TRIM24 (tripartite motif containing 24); EGFR (epidermal growth factor receptor); Bcl2 (B‐cell lymphoma 2); Bcl‐xL (B‐cell lymphoma‐extra large); SMARCA2/4 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member); IRAK4 (interleukin‐1 receptor‐associated kinase 4); STAT3 (Signal transducer and activator of transcription 3).