Carfilzomib is a second generation proteasome inhibitor that has been used in oncology research.Being a derivative of epoxomicin, carfilzomib has a tetrapeptide epoxyketone structure.
The anti-cancer activity of carfilzomib on proteasomes is attributed to irreversibly binding to a 20S subunit on proteasomes. Affinity of carfilzomib for the subunit has been shown to be fairly significant, allowing carfilzomib to be effective at targeting multiple myeloma and lymphoma.
Proteasomes degrade excess or damaged proteins in both the nucleus and cytosol by cleaving hydrophobic residue peptide bonds. When proteasomes are inhibited by carfilzomib, polyubiquinated proteins accumulate. Polyubiquinated proteins will upregulate p21 synthesis, which activates cell cycle arrest and eventually apoptosis.
Carfilzomib has also been shown to have poor solubility in aqueous solutions, but greater solubility in organic solvents such as DMSO. Aqueous solubility can be enhanced by diluting carfilzomib-organic solvent solution in aqueous buffers. Using aqueous carfilzomib in biological settings should be done in dilute concentrations to limit organic solvent presence. Because carfilzomib organic-aqueous solutions only have a shelf life of approximately 24 hours, it is recommended to make small portions for immediate use.
MW: 719.91 g/mol
Storage/Handling: Store at 4°C.
Soluble in DMSO.
PubChem Chemical ID: 11556711
|Storage/Handling||Store at 4°C.|