title: Carfilzomib: a novel second-generation proteasome inhibitor.
abstract: Carfilzomib (formerly PR-171) is a novel epoxyketone-based irreversible proteasome inhibitor. In preclinical studies, carfilzomib demonstrated irreversible binding to the proteasome and minimal off-target inhibition of other proteases. In clinical studies carfilzomib has demonstrated substantial antitumor activity in hematologic malignancies while exhibiting a well-tolerated side-effect profile. Painful neuropathy was minimally reported, suggesting a possible advantage over other proteasome inhibitors. With single-agent carfilzomib, dose-limiting toxicity was hematologic and included thrombocytopenia and neutropenia. In patients with relapsed or refractory multiple myeloma, twice-weekly consecutive-day single-agent carfilzomib 20 mg/m(2) for 3 weeks every 28 days, escalating to 27 mg/m(2) the second cycle was associated with a 54% overall response rate in bortezomib-naive patients and a 26% overall response rate in bortezomib and immunomodulatory drug refractory patients.
authors.affiliation: Mayo Clinic in Arizona, Division of Internal Medicine, Scottsdale, AZ 85259, USA.
authors.forename: Meaghan L
authors.initials: ML
authors.lastname: Khan
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D019337:Hematologic Neoplasms / Q000188:drug therapy*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011485:Protein Binding; D011719:Pyrazines / Q000627:therapeutic use; D013921:Thrombocytopenia
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D009842:Oligopeptides; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; C524865:carfilzomib