Abstract
On 13 May 2003, Bortezomib (Velcade; Millenium) became the first proteasome inhibitor to be approved by the US FDA. Bortezomib was approved for multiple myeloma, a blood cancer that affects two to three people per 100,000, in record time — four months — on the basis of positive outcomes in early-phase trials.
References
Coux, O., Tanaka, K. & Goldberg, A. L. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65, 801–847 (1996).
King, R. W., Deshaies, R. J., Peters, J. -M. & Kirschner, M. W. How proteolysis drives the cell cycle. Science 274, 1652–1659 (1996).
Kisslev, A. F. & Goldberg, A. L. Proteasome inhibitors: from research tools to drug candidates. Chem. Biol. 121, 1–20 (2001).
Hideshima, T. et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis and overcomes drug resistance in human multiple myeloma cells. Cancer Res. 61, 3071–3076 (2001).
Barnes, P. J. & Karin, M. Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases. N. Engl. J. Med. 336, 1066–1071 (1997).
Palombella, V. J., Rando, O. J., Goldberg, A. L. & Maniatis, T. The ubiquitin-proteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB. Cell 78, 773–785 (1994).
Adams, J. Proteasome inhibition in cancer: development of PS-341. Semin. Oncol. 28, 613–619 (2001).
Adams, J. et al. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg. Med. Chem. Lett. 8, 333−338 (1998).
Anderson, P. G. A Phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med. 348, 2609–2617 (2003).
FDA Drug Approvals List [online] (cited 13 May 2003) <http://www.fda.gov/cder/foi/label/2003/021602lbl.pdf> (2003).
Zangari, M. et al. Marked activity also in Del 13 multiple myeloma (MM) of PS-341 (PS) and subsequent thalidomide (THAL) in a setting of resistance to post-autotransplant salvage therapies. Proc. Am. Soc. Hematol. A387 (2002).
Orlowski, R. Z. et al. Phase I study of the proteasome inhibitor bortezomib (PS-341, ValcadeTM) in combination with pegylated liposomal doxorubicin (DoxilTM) in patients with refractory hematological malignancies. Proc. Am. Soc. Hematol. A388 (2002).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Paramore, A., Frantz, S. Bortezomib. Nat Rev Drug Discov 2, 611–612 (2003). https://doi.org/10.1038/nrd1159
Issue Date:
DOI: https://doi.org/10.1038/nrd1159
- Springer Nature Limited
This article is cited by
-
Cooperative NF-κB and Notch1 signaling promotes macrophage-mediated MenaINV expression in breast cancer
Breast Cancer Research (2023)
-
Clonal heterogeneity in ER+ breast cancer reveals the proteasome and PKC as potential therapeutic targets
npj Breast Cancer (2023)
-
Characterizing dry mass and volume changes in human multiple myeloma cells upon treatment with proteotoxic and genotoxic drugs
Clinical and Experimental Medicine (2023)
-
Severe cellular stress activates apoptosis independently of p53 in osteosarcoma
Cell Death Discovery (2021)
-
Cellulosic CuI Nanoparticles as a Heterogeneous, Recyclable Catalyst for the Borylation of α,β-Unsaturated Acceptors in Aqueous Media
Catalysis Letters (2021)