Table 3.
Drugs that may regulate the immune checkpoint pathways through targeting ubiquitination/deubiquitination (clinical)
| Type | Name | Target | Developer | Implications | Stage |
|---|---|---|---|---|---|
| Proteasome inhibitors |
Bortezomib (Velcade, PS-341, MLN-341) |
20S core subunit |
Millennium |
Relapsed and/or refractory multiple myeloma; mast cell leukemia |
Approved |
|
Carfilzomib (Kyprolis, PR-171) |
20S core subunit |
ONYX |
Relapsed and/or refractory multiple myeloma |
Approved | |
|
Ixazomib (Ninlaro, MLN-9708) |
20S core subunit |
Millennium |
Relapsed and/or refractory multiple myeloma; acute myeloid leukemia; follicular lymphoma; peripheral T-cell lymphoma |
Approved | |
|
Marizomib (NPI-0052, Salinosporamide A) |
20S core subunit |
Nereus |
Relapsed and/or refractory multiple myeloma; non-small cell lung cancer; pancreatic cancer; melanoma; lymphoma; ependymoma; glioblastoma |
Phase 3 | |
|
Oprozomib (ONX-0912, PR-047) |
20S core subunit |
ONYX |
Multiple myeloma; Waldenstrom Macroglobulinemia; solid tumors; advanced non-central nervous system malignancies |
Phase 1/2 | |
|
Delanzomib (CEP-18770) |
20S core subunit |
Cephalon |
multiple myeloma; solid tumors; non-Hodgkin lymphoma |
Phase 1/2 | |
| E1 inhibitors |
MLN-7243 (TAK-243) |
Ubiquitin E1 enzyme |
Millennium |
myelodysplastic syndrome; acute myeloid leukemia; myelomonocytic leukemia; advanced malignant solid tumors |
Phase 1 |
|
Pevonedistat (MLN-4924, TAK-924) |
NEDD8 activating enzyme |
Millennium |
Acute myeloid leukemia; myelodysplastic syndrome; plasma cell myeloma; metastatic melanoma; solid tumors |
Phase 3 | |
| E3 inhibitors |
Lenalidomide (Revlimid) |
MARCH 1 | Celgene |
Multiple myeloma; myelodysplastic syndromes; mantle cell lymphoma |
Approved |