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Carfilzomib is a selective, irreversible proteasome inhibitor (over 80% inhibition at doses of 10 nM and above). In models of multiple myeloma, Carfilzomib potently bound and specifically inhibited the chymotrypsin-like proteasome and immunoproteasome activities, resulting in accumulation of ubiquitinated substrates. It induced a dose- and time-dependent inhibition of proliferation, ultimately leading to apoptosis. It also inhibited proliferation and activated apoptosis in patient-derived MM cells and neoplastic cells from patients with other hematologic malignancies. Carfilzomib showed increased efficacy compared with bortezomib and was active against bortezomib-resistant MM cell lines and samples from patients with clinical bortezomib resistance. Currently it is approved by US FDA for relapsed and refractory multiple myeloma in 2012.

How to Use:

• In vitro: Carfilzomib was used at 0.1 μM in vitro and in cellular assays.
• In vivo: Carfilzomib was dosed to mice/rats by intravenous administration at 0.5-4 mg/kg once per day.

Reference:

1. 1. Kuhn DJ, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. (2007) Blood. 110(9):3281-90.
2. 2. Parlati F,et al. Carfilzomib can induce tumor cell death through selective inhibition of the chymotrypsin-like activity of the proteasome. (2009) Blood.114(16):3439-47.
3. 3. Dasmahapatra G, et al. Carfilzomib interacts synergistically with histone deacetylase inhibitors in mantle cell lymphoma cells in vitro and in vivo. (2011) Mol Cancer Ther. 10(9):1686-97.
4. 4. Sacco A, et al. Carfilzomib-dependent selective inhibition of the chymotrypsin-like activity of the proteasome leads to antitumor activity in Waldenstrom's Macroglobulinemia. (2011) Clin Cancer Res. 17(7):1753-64.

Products are for research use only. Not for human use.