Proteasome inhibitors are a class of drugs that block the action of proteasomes, cellular complexes responsible for degrading unneeded or damaged proteins. This inhibition can lead to the accumulation of misfolded proteins, triggering cell death, particularly in cancer cells, making them valuable in oncology.
Several key drugs are recognized as proteasome inhibitors, each with distinct mechanisms of action and characteristics:
Overview of Proteasome Inhibitors
| Name (Brand Name) | Kinetics | Active Moiety |
|---|---|---|
| Bortezomib (Velcade®) | Slowly reversible inhibitor β5>β1>β2 | Boronate |
| Carfilzomib (Kyprolis®) | Irreversible inhibitor β5>β2/β1 | Epoxyketone |
| Ixazomib (Ninlar®) | Reversible inhibitor β5>β1 | Boronate |
Detailed Information on Specific Proteasome Inhibitors
- Bortezomib (Velcade®): This was the first proteasome inhibitor approved for clinical use. It acts as a slowly reversible inhibitor, primarily targeting the β5 subunit of the proteasome, though it also affects β1 and β2 subunits. Its active component is a boronate group, which forms a covalent bond with the proteasome. Bortezomib is widely used in the treatment of multiple myeloma and mantle cell lymphoma.
- Carfilzomib (Kyprolis®): An advanced proteasome inhibitor, carfilzomib is an irreversible inhibitor, meaning it forms a permanent bond with its target. It shows high selectivity for the β5 subunit but also impacts β2 and β1. Its mechanism involves an epoxyketone functional group. Carfilzomib is approved for treating relapsed or refractory multiple myeloma.
- Ixazomib (Ninlaro®): Unique among the listed drugs, ixazomib is an oral, reversible inhibitor. Like bortezomib, its active component is a boronate and it primarily targets the β5 subunit, with some activity against β1. Its oral bioavailability makes it a convenient option for patients with multiple myeloma, often used in combination therapies.
These drugs represent significant advancements in cancer therapy, particularly for hematological malignancies, by disrupting cellular protein homeostasis and inducing apoptosis in malignant cells.
