Bortezomib
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Bortezomib
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| Systematic (IUPAC) name | |
| [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2- [(pyrazinylcarbonyl)amino]propyl]amino]butyl] boronic acid |
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| Identifiers | |
| CAS number | |
| ATC code | L01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C19H25N4O4 |
| Mol. mass | 384.24 g/mol |
| Pharmacokinetic data | |
| Bioavailability | n/a |
| Protein binding | 83% |
| Metabolism | Hepatic, CYP extensively involved |
| Half life | 9 to 15 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
D(US) |
| Legal status |
℞ Prescription only |
| Routes | Intravenous |
Bortezomib (originally PS-341 and marketed as Velcade™ by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is the best studied of a next generation of anti-myeloma drugs, and is being studied for other hematologic cancers and solid tumors. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
The boron atom in bortezomib binds the catalytic site of the 26S proteasome with high affinity and specificity. In normal cells, the proteasome regulates protein expression and function by degradation of ubiquinated proteins, and also cleanses the cell of abnormal or misfolded proteins. Clinical and preclinical data support a role in maintaining the immortal phenotype of myeloma cells, and cell-culture and xenograft data support a similar function in solid tumor cancers. While multiple mechanisms are likely to be involved, proteasome inhibition may prevent degradation of pro-apoptotic factors, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways.
The Multiple Myeloma Research Foundation was responsible for a substantial amount of the funding for the development and testing of this drug. [1]
[edit] Side effects
Bortezomib is associated with peripheral neuropathy in 30% of patients; occasionally, it can be painful. This can be worse in patients with pre-existing neuropathy. In addition, myelosuppression as neutropenia and thrombocytopenia can also occur and be dose limiting. However, relative to other treatment options for patients with advanced disease (eg, bone marrow transplantation), these side effects are mild.
[edit] External links
- Millennium Pharmaceuticals website on Velcade™
- Multiple Myeloma Research Foundation article on Velcade™
- International Myeloma Foundation article on Velcade™
- U.S. Food and Drugs Administration on Velcade™
- Dedicated website for European audience
