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Bortezomib

Name: Bortezomib
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. 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). Drug type: Approved. Investigational. Small Molecule. Drug category: Antineoplastic Agents. Protease Inhibitors
Synonym(s): bortezomib, Velcade
Has role: Drug
Super-category: Molecular entity
URL: http://www.drugbank.ca/drugs/DB00188
*Id: CHEBI:52717
Related to: 26S proteasome non-ATPase regulatory subunit 1, 26S proteasome non-ATPase regulatory subunit 2, Proteasome subunit beta type 1, Proteasome subunit beta type 5, Proteasome subunit beta type 2
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Facts about BortezomibRDF feed
Commenttaken from DrugBank
CurationStatusuncurated  +
CuratorAb  +
DefiningCitationhttp://www.drugbank.ca/drugs/DB00188  +
DefinitionBortezomib (originally PS-341 and marketed 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. 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). Drug type: Approved. Investigational. Small Molecule. Drug category: Antineoplastic Agents. Protease Inhibitors Antineoplastic Agents. Protease Inhibitors
Has roleDrug  +
IdCHEBI:52717  +
LabelBortezomib  +
ModifiedDate12 August 2014  +
RelatedTo26S proteasome non-ATPase regulatory subunit 1  +, 26S proteasome non-ATPase regulatory subunit 2  +, Proteasome subunit beta type 1  +, Proteasome subunit beta type 5  +, and Proteasome subunit beta type 2  +
SuperCategoryMolecular entity  +
Synonymbortezomib  +, and Velcade  +