Table 1.
Proteasome, E1, E3, or DUB modulators in clinic use or in (pre)-clinical development
| Target | Compound ID | Structure | Highest clinical stage and status1 | Reference |
|---|---|---|---|---|
| Proteasome inhibitors | ||||
| proteasome | Bortezomib |  | FDA approved | Teicher et al. [33] |
| Carfilzomib |  | FDA approved | Kim and Crews [34] | |
| Ixazomib |  | FDA approved | Kupperman et al. [35] | |
| Oprozomib |  | Phase 1/Phase 2, completed | Chauhan et al. [36] | |
| Delanzomib |  | Phase 1/Phase 2, terminated | Piva et al. [37] | |
| Marizomib |  | Phase 3, recruiting | Potts et al. [38] | |
| E1 modulator | ||||
| UAE (Uba1) | TAK-243 |  | Phase 1, completed | Milhollen et al. [39] Hyer et al. [40] |
| E3 modulators | ||||
| CRBN | Thalidomide |  | FDA approved | Ito et al. [41] |
| Lenalidomide |  | FDA approved | Krönke, et al. [42, 43] | |
| Pomalidomide |  | FDA approved | Fischer et al. [44] | |
| Avadomide |  | Phase 1/Phase 2, active | Rasco et al. [45] | |
| Iberdomide |  | Phase 1/Phase 2, recruiting | Bjorklund et al. [46] | |
| MDM2 | APG-115 |  | Phase 1/Phase 2, recruiting | Rasco et al. [47] |
| CGM097 |  | Phase 1, active | Holzer et al. [48] | |
| Cul4-DCAF15 | Tasisulam |  | Phase 3, terminated | Han et al. [49] |
| Indisulam |  | Phase 2, completed | ||
| NSC-339004 |  | Phase 2, Completed | ||
| Keap1 | Bardoxolone methyl |  | Phase 3, recruiting | Gross et al. [50] |
| Omaveloxolone |  | Phase 2, completed | Lynch et al. [51] | |
| Deubiquitinase inhibitors | ||||
| USP14 > UCH37; many other DUBs inhibited | VLX1570 |  | Phase 1/Phase 2, prematurely ended | Paulus et al. [52] |
| Target | Compound ID | Structure | Highest clinical stage and status1 | Reference |
|---|---|---|---|---|
| Proteasome inhibitors | ||||
| proteasome | Bortezomib | | FDA approved | Teicher et al. [33] |
| Carfilzomib | | FDA approved | Kim and Crews [34] | |
| Ixazomib | | FDA approved | Kupperman et al. [35] | |
| Oprozomib | | Phase 1/Phase 2, completed | Chauhan et al. [36] | |
| Delanzomib | | Phase 1/Phase 2, terminated | Piva et al. [37] | |
| Marizomib | | Phase 3, recruiting | Potts et al. [38] | |
| E1 modulator | ||||
| UAE (Uba1) | TAK-243 | | Phase 1, completed | Milhollen et al. [39] Hyer et al. [40] |
| E3 modulators | ||||
| CRBN | Thalidomide | | FDA approved | Ito et al. [41] |
| Lenalidomide | | FDA approved | Krönke, et al. [42, 43] | |
| Pomalidomide | | FDA approved | Fischer et al. [44] | |
| Avadomide | | Phase 1/Phase 2, active | Rasco et al. [45] | |
| Iberdomide | | Phase 1/Phase 2, recruiting | Bjorklund et al. [46] | |
| MDM2 | APG-115 | | Phase 1/Phase 2, recruiting | Rasco et al. [47] |
| CGM097 | | Phase 1, active | Holzer et al. [48] | |
| Cul4-DCAF15 | Tasisulam | | Phase 3, terminated | Han et al. [49] |
| Indisulam | | Phase 2, completed | ||
| NSC-339004 | | Phase 2, Completed | ||
| Keap1 | Bardoxolone methyl | | Phase 3, recruiting | Gross et al. [50] |
| Omaveloxolone | | Phase 2, completed | Lynch et al. [51] | |
| Deubiquitinase inhibitors | ||||
| USP14 > UCH37; many other DUBs inhibited | VLX1570 | | Phase 1/Phase 2, prematurely ended | Paulus et al. [52] |
1
Data from ClinicalTrials.gov and EU Clinical Trials Register.