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Description: Bortezomib (originally PS-341 and marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
Drug Type: Small Molecule; Approved; Investigational
Pharmacology: Bortezomib is a drug that inhibits the mammalian 26S proteasome. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro. Bortezomib causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma. Tumor cells, that is, rapidly dividing cells, appear to be more sensitive to proteasome inhibition.
Mechanism of Action: Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The active site of the proteasome has chymotrypsin-like, trypsin-like, and postglutamyl peptide hydrolysis activity. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Bortezomib is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. In addition, bortezomib appears to increase the sensitivity of cancer cells to traditional anticancer agents (e.g., gemcitabine, cisplatin, paclitaxel, irinotecan, and radiation).
Indication: For treatment of multiple myeloma in patients who have not been successfully treated with at least two previous therapies.
Half Life: The mean elimination half-life of bortezomib after first dose ranged from 9 to 15 hours at doses ranging from 1.45 to 2.00 mg/m2 in patients with advanced malignancies.
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Data Correlations | 6 studies

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Genes category icon Genes
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PSMD1 100 100
PSMD2 100 100
FAM20B 100 100
CTAG2 98 98
PAG1 97 97
387763 96 96
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Biogroups category icon Biogroups
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MAGE protein 100 100
Hematopoietic Cell Lineage 99 99
Proteasome 98 98
Immunoglobulin subtype 98 98
Cell Adhesion Molecules (CAMs) 98 98
Cyanoamino Acid Metabolism 98 98
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Individual Studies

  • Molecular targets of proteasome inhibitor, bortezomib, on ATL cells

    Homo sapiens Homo sapiens | RNA Expression   RNA Expression

    Adult T-cell leukemia (ATL) is a fatal neoplasia derived from HTLV-1 infected T lymphocytes exhibiting constitutive activation of NF-kB. To elucidate the complex molecular mechanism of anti-tumor effect of the proteasome inhibitor, bortezomib in ATL cells, we attempted to perform gene expression pro…

    Authors: Ohyashiki JH

    Organization: Tokyo Medical University Intractable Imm…

  • Drug target sets for approved compounds

    Homo sapiens Homo sapiens | Therapeutic   Therapeutic

    The DrugBank database is a unique bioinformatics and cheminformatics resource that combines detailed drug (i.e. chemical, pharmacological and pharmaceutical) data with comprehensive drug target (i.e. sequence, structure, and pathway) information.

    Authors: David S Wishart, Craig Knox, An Chi Guo et al.

    Organization: Department of Computing Science, Univers…
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Associated Researchers

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Thought leaders and organizations working on research involving ps-341.

View All Author iconAuthors
  • Kenneth C Anderson
  • Teru Hideshima
  • Dharminder Chauhan
  • Klaus Podar
  • Constantine Mitsiades
View All Clinical trial sponsors icon Clinical Trials Sponsors
  • Millennium Pharmaceuticals, Inc.
  • Mayo Clinic
  • M.D. Anderson Cancer Center
  • Memorial Sloan-Kettering Cancer Center
  • University of Wisconsin, Madison
View All Affiliations icon Organizations
  • Dana-Farber Cancer Institute
  • Dana-Farber Cancer Institute and Harvard Medical School
  • Washington University School of Medicine
  • Emory University School of Medicine
  • Zhejiang University

Clinical Trials | 127 trials

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