Table 1.
Immunoproteasome inhibitors in pre-clinical and clinical development.
| Inhibitor | Developed by | Backbone | Target | Binding Kinetics |
|---|---|---|---|---|
| UK-101 | [148] | Peptidyl epoxyketone | β1i subunit (144-fold more selective than β1, but only 10-fold to β5) | Covalent irreversible |
| ONX-0914 (PR-957) | [45] | Peptidyl epoxyketone | β5i subunit (20- to 40-fold more selective than β5 or β1i) | Covalent irreversible |
| IPSI-001 | [44] | Peptidyl aldehyde | β1i subunit (100-fold more selective than β1) | Covalent reversible |
| PR-924 | [41] | Peptidyl epoxyketone | β5i subunit (130-fold more selective than β5) | Covalent irreversible |
| LU-001i | [154] | Peptidyl epoxyketone | β1i subunit (925-fold more selective than β1) | Covalent irreversible |
| LU-015i | [154] | Peptidyl epoxyketone | β5i subunit (553-fold more selective than β5) | Covalent irreversible |
| LU-035i | [154] | Peptidyl epoxyketone | β5i subunit (500-fold more selective than β5) | Covalent irreversible |
| HT2210 and HT2106 | [155] | Oxathiazole | β5i subunit (>4700-fold more selective than β5c) | Covalent irreversible |
| 1-CA and 4-CA | [156] | Peptidyl epoxyketone | β5i subunit (75- to 150-fold more selective than β5) | Covalent irreversible |
| PKS2279 and PKS2252 | [157] | N,C-capped dipeptide | β5i subunit (5600 and 13,600-fold more selective than β5) | Non-covalent |
| KZR-504 | [158] | Peptidyl epoxyketone | β1i subunit (925-fold more selective than β1) | Covalent irreversible |
| KZR-616 | [158] | Peptidyl epoxyketone | β5i and β1i subunits (18- and 81-fold more selective than β5 and β1c) | Covalent irreversible |
| LU-002i | [159] | Peptidyl epoxyketone | β2i subunit | Covalent irreversible |
| M3258 | [160] | Boronic acid | β5i subunit (>500-fold more selective than β5) | Covalent reversible |