Table 1.
An overview of the recruiting mechanism-specific degraders in relation to their target protein, disease and degradation efficiency.
| Type of Degrader | Degrader Name | Degrader Target | Disease | DC50 a (nM) | Reference |
|---|---|---|---|---|---|
| Cereblon-recruiting PROTACs: | dBET1 | BRD4 | Cancer (MM, AML) | 430.0 | Winter, et al. [26] |
| TD-428 | BRD4 | Cancer (MM) | 32.0 × 10−2 | Kim, et al. [24] | |
| ARV-825 | BRD4 | Cancer (Burkitt lymphoma) | 1.0 | Lu, et al. [28] | |
| BETd-246 | BRD4 | Cancer (breast) | 10.0 | Bai, et al. [27] | |
| Compound 21 | BRD4 | Cancer (MM, AML) | 3.7 × 10−2 | Zhou, et al. [31] | |
| Compound 23 | BRD4 | 5.1 × 10−2 | |||
| dBRD9 | BRD9 | Cancer (AML) | 104.0 | Remillard, et al. [32] | |
| GSK983 | PCAF | Anti-inflammatory diseases | 1.5 | Bassi, et al. [33] | |
| GCN5 | 3.0 | ||||
| DAS-6-2-2-6-CRBN | cAbl | Cancer (chronic myelogenous leukemia) | 25.0 | Lai, et al. [34] | |
| Bcr-Abl | |||||
| TL12-186 | CDK2 | Cancer, rheumatoid arthritis, and idiopathic pulmonary fibrosis | 73.0 | Huang, et al. [18] | |
| CDK9 | 55.0 | ||||
| CRBN-PROTAC 2 | p38δ | Cancer and Diabetes | 27.0 | Bondeson, et al. [16] | |
| MT-802 | BTK | Chronic lymphocytic leukemia | 9.1 | Buhimschi, et al. [35] | |
| pomalidomide-Vorinostat | HDAC6 | Cancer (AML, ovarian, hepatocellular carcinomas) | 32.0 | Yang, et al. [39] | |
| VHL-recruiting PROTACs: | MZ1 | BRD4 | Cancer (NSCLC) | 1000.0 | Zhong, et al. [65] |
| ARV-771 | BRD4 | Cancer (castration-resistant prostate cancer) | 5.0 | Raina, et al. [46] | |
| VZ185 | BRD9 | Cancer (cervical, NSCLC) | 4.0 | Zoppi, et al. [47] | |
| BRD7 | 34.0 | ||||
| ACBI1 | SMARCA2 | Cancer (AML) | 6.0 | Farnaby, et al. [48] | |
| SMARCA4 | 11.0 | ||||
| PBRM1 | 32.0 | ||||
| PROTAC_RIPK2 | RIPK2 | Auto-inflammatory diseases (Blau syndrome, early-onset sarcoidosis) | 1.4 | Bondeson, et al. [49] | |
| PROTAC_ERRα | ERRα | Cancer (breast) | 100.0 | ||
| VHL-PROTAC 1 | p38α | Cancer | 210.0 | Bondeson, et al. [16] | |
| SJFα | p38α | 7.2 | Smith, et al. [19] | ||
| SJFδ | p38δ | Cancer and diabetes | 46.2 | ||
| VHL-lapatinib | EGFR | Cancer (glioblastoma multiforme, NSCLC) | 39.2 | Burslem, et al. [17] | |
| VHL-gefitinib | 11.7 | ||||
| VHL-afatinib | 215.8 | ||||
| VHL-lapatinib | HER2 | 102.0 | |||
| VHL-Foretinib | c-MET | 66.7 | |||
| PROTAC-3 | Fak | Cancer (malignant pleural mesothelioma, ovarian) | 3.0 | Cromm, et al. [50] | |
| Nondisclosed recruiting PROTACs: | ARV-471 | ERα | Cancer (breast) | 2.0 | Flanagan, et al. [52] |
| AR PROTAC | AR | Cancer (prostate) | 1.0 | Neklesa, et al. [53] | |
| SNIPERs: | SNIPER(CRABP-I) | CRABP-I | ~10,000.0 b | Itoh, et al. [57] | |
| SNIPER(ERα)-87 | ERα (MCF-7 cells) |
Cancer (breast) | 3.0 | Ohoka, et al. [61] | |
| ERα (T47D cells) |
Cancer (breast) | 9.6 | |||
| SNIPER(TACC3) | TACC3 | Cancer (ovarian, breast, squamous cell carcinoma, lymphoma) |
~10,000.0 b | Ohoka, et al. [62] | |
| SNIPER(ABL)-38 | cABL/BCR-ABL | Cancer (chronic myelogenous leukemia, MM, AML) | 30.0 | Ohoka, et al. [61] | |
| SNIPER(BRD4)-1 | BRD4 | 10.0 | |||
| SNIPER(PDE4)-9 | PDE4 | 10.0 b | |||
| MDM2-recruiting PROTACs: | A1874 | BRD4 | Cancer (MM, AML) | 32.0 | Hines, et al. [69] |
| UP independent HyT degraders: | SARD279 | AR | Cancer (prostate) | 1000.0 | Gustafson, et al. [11] |
| SARD033 | 2000.0 | ||||
| CMA-recruiting degraders: | TAT-GluN2Bct-PP | DAPK1 | Neuroprotectivity (stroke) | ~50,000.0 b | Fan, et al. [79] |
a DC50: the concentration where 50% of the protein has been degraded; b The DC50 value was not given but inferred from experimental results. HyT, Hydrophobic tag. MM, multiple myeloma; AML, acute myeloid leukemia; NSCLC, non-small cell lung cancer.