The ubiquitin-proteasome system (UPS) is the essential system within the body to ensure elimination of misfolded proteins.1 Proteins which are to be degraded are tagged with polyubiquitin chains, which are recognized by 19S.1 This particle, 19S, along with the 20S proteasome core, form the 26S proteasome overall.1 One protein the 20S proteasome targets for degradation is p53, a tumor suppressor gene.2 When the 20S proteasome is not functioning correctly, there is an increase in p53 levels which can lead to mutated forms of p53 that can lead to a variety of cancers.2 Proteasome inhibitors (PI) work as cancer treatment by targeting proteasome activity by binding with the 20S proteasome to prevent protein degredation.2
Understanding the Role of 20S Proteasome
This animation explains the role of the 20S proteasome in regulating the cellular life cycle and the effects of disruptions in the ubiquitin proteasome system.
Proteasome Inhibitors
Proteasome inhibitors target the proteasome function in tumor cells. This table outlines therapies targeting the 20S proteasome both approved by the FDA and in the pipeline.
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Proteasome Inhibitors Approved by the FDA |
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Brand Name (Generic Drug Name) |
Indications |
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Ninlaro (ixazomib)1 |
Treatment in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior therapy |
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Velcade (bortezomib)2 |
Treatment of adult patients with multiple myeloma |
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Treatment of adult patients with mantle cell lymphoma |
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Kyprolis (carfilzomib)3 |
Treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 lines of therapy in combination land dexamethasone; dexamethasone; daratumumab and dexamethasone; daratumumab and hyaluronidase-fihj and dexamethasone; or isatuximab and dexamethasone. |
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Treatment as monotherapy for patients with relapsed or refractory multiple myeloma who have received 1 or more lines of therapy |
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Proteasome Inhibitors in the Pipeline |
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Marizomib4 |
Treatment being evaluated in glioblastoma |
