A selective and irreversible proteasome inhibitor used in multiple myeloma. Trials are taking place with combination therapy with dexamethasone and/or lenalidomide and/or melphalan and/or panobinostat. There is also interest in the combination with kinesin spindle protein inhibitors. It has enhanced inhibition of proteasome function compared to first generation proteasome inhibitors and this leads to the accumulation of proteins targeted for degradation and subsequent cellular apoptosis.
Less neuropathy but perhaps worse cardiac toxicity compared to other proteasome inhibitors
Cautions and Interactions
- Cardiac failure
Carfilzomib is an irreversible, epoxyketone proteasome inhibitor that targets the rate limiting chymotrypsin-like activity of the proteasome subunit beta type-5 component of the 20S proteasome catalytic core of the proteasome. It is a derivative of poxomicin, a natural product isolated from actinomycetes. It forms an irreversible, selective, and highly specific adduct with the N-terminal threonine of proteasome subunit beta type-5.
- ↑ Sugumar D, Keller J, Vij R. Targeted treatments for multiple myeloma: specific role of carfilzomib. Pharmacogenomics and personalized medicine. 2015; 8:23-33.(Epub) (Link to article – subscription may be required.)
- ↑ Berdeja JG, Hart LL, Mace JR, Arrowsmith ER, Essell JH, Owera RS, Hainsworth JD, Flinn IW. Phase I/II Study of the Combination of Panobinostat and Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma. Haematologica. 2015 Feb 20.(Epub ahead of print) (Link to article – subscription may be required.)