Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma.[1] This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications.[2] See also Bortezomib.
Bortezomib is an N-protected dipeptide and can be written as , which stands for instead of a carboxylic acid.
The boron atom in bortezomib binds the catalytic site of the 20S proteasome[3] with high affinity and specificity.
- (2f16).
- .
- . Interacting residues are labeled.
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In normal cells, the proteasome regulates protein expression and function by degradation of ubiquitylated proteins, and also rids the cell of abnormal or misfolded proteins. Clinical and preclinical data support a role for the proteasome 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, thereby triggering programmed cell death in neoplastic cells. Recently, it was found that bortezomib caused a rapid and dramatic change in the levels of intracellular peptides that are produced by the proteasome.[4] Some intracellular peptides have been shown to be biologically active, and so the effect of bortezomib on the levels of intracellular peptides may contribute to the biological and/or side effects of the drug.
