Table 3.
Summary of UPS inhibitors which are FDA-approved and/or tested in clinical trials described in this review.
| Inhibitor | Target | Cancer Type | Clinical Trial | Reference |
|---|---|---|---|---|
| Bortezomib | Proteasomal inhibitor | Multiple myeloma, Mantle cell lymphoma, Leukemia, Neuroblastoma, Head and Neck, Thyroid, Hepatocellular |
FDA approved |
www.clinicaltrials.gov [126,166,167,169,170,171,172,177] |
| Carfilzomib | Proteasomal inhibitor | Multiple myeloma, Lymphoma, Relapsed and/or refractory multiple myeloma, Leukemia, Lung, Thyroid, Refractory renal cell carcinoma |
FDA approved |
www.clinicaltrials.gov [54,173,174,175,176,177] |
| Ixazomib | Proteasomal inhibitor | Multiple myeloma, Relapsed and/or refractory multiple myeloma, Lymphoma, Leukemia, Breast, Glioblastoma, Renal cell carcinoma, Hodgkin and T cell lymphoma |
FDA approved |
www.clinicaltrials.gov [178] |
| Delanzomib | Proteasomal inhibitor | Non-Hodgkin’s lymphoma | Phase I | www.clinicaltrials.gov |
| Marizomib | Proteasomal inhibitor | Multiple myeloma, Advanced solid tumors | Phase I/II | www.clinicaltrials.gov |
| Oprozomib | Proteasomal inhibitor | Multiple myeloma, Glioma, Pancreatic, Lung, Melanoma, Lymphoma, Glipblastoma | Phase I/II/III | www.clinicaltrials.gov |
| MLN4924 | NAE and UBA1(E1) | Advanced malignant solid tumors, Melanoma, Hepatocellular, B cell lymphoma, Hematologic malignancies, Acute myelocytic leukemia |
Phase I/II/III | www.clinicaltrials.gov |
| TAK981 | SAE (E1) | B cell lymphoma, colorectal, non-Hodgkin’s, Advcnced/metasiatic solid tumors | Phase I/II | www.clinicaltrials.gov |
| TAS4464 | NAE (E1) | Multiple myeloma, non-Hodgkin lymphoma | Phase I/II | www.clinicaltrials.gov |
| SAR-405838 | MDM2 (E2) | Solid tumors | Phase I |
www.clinicaltrials.gov [172,183] |
| CGM-097 | MDM2 (E2) | Advanced p53 wildtype solid tumors | Phase I |
www.clinicaltrials.gov [184,185] |
| DS-3032b | MDM2 (E2) | Acute myelocytic leukemia | Phase I/II |
www.clinicaltrials.gov [186,187] |
| Debio1143 (AT-406) | cIAP1/2 (E3) | Acute myeloid leukemia | Phase I |
www.clinicaltrials.gov [188] |
| LC-161 | IAP (E3) | Advanced solid tumors | Phase I |
www.clinicaltrials.gov [189] |
| Birinapant | IAP (E3) | Solid tumors | Phase I/II |
www.clinicaltrials.gov [190] |
| Pimozide | USP1 | Glioma, Non-small cell lung cancer | FDA approced for Tourette’s syndrome; Preclinical | [191,192] |
| Mitoxantrone | USP11 | Metastatic crastrate -resistant prostate, Acute myeloid leukemia, Advanced breast cancer, non-Hodgkin’s lymphoma, Primary liver |
FDA approved | [193,194,195,196,197,198,199,200,201] |