Carfilzomib (CFZ)

Carfilzomib is a tetrapeptide epoxyketone and a selective proteasome inhibitor. It is an analog of epoxomicin. Carfilzomib is derived from epoxomicin, a natural product that was shown by the laboratory of Craig Crews at Yale University to inhibit the proteasome. Carfilzomib irreversibly binds to and inhibits the chymotrypsin-like activity of the 20S proteasome, an enzyme that degrades unwanted cellular proteins. Inhibition of proteasome-mediated proteolysis results in a build-up of polyubiquinated proteins, which may cause cell cycle arrest, apoptosis, and inhibition of tumor growth. carfilzomib had a 53 percent overall response rate among patients with relapsed and/or refractory multiple myeloma who had not previously received bortezomib. This study also included a bortezomib-treated cohort. Results were reported separately.