Bortezomib
From Proteopedia
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*<scene name='10/1022872/Cv/5'>20S proteasome bound with 6 molecules of bortezomib</scene>. | *<scene name='10/1022872/Cv/5'>20S proteasome bound with 6 molecules of bortezomib</scene>. | ||
*<scene name='10/1022872/Cv/6'>Bortezomib binding site</scene>. Interacting residues are labeled. | *<scene name='10/1022872/Cv/6'>Bortezomib binding site</scene>. Interacting residues are labeled. | ||
| - | *<scene name='10/1022872/Cv/7'>The catalytic threonine residue is covalently bound to bortezomib and its activity is blocked</ | + | *<scene name='10/1022872/Cv/7'>The catalytic threonine residue is covalently bound to bortezomib and its activity is blocked</scene>. |
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.<ref name="a16">PMID:23308178</ref> 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. | 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.<ref name="a16">PMID:23308178</ref> 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. | ||
Revision as of 14:15, 15 January 2024
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References
- ↑ "Bortezomib Monograph for Professionals". Drugs.com. Retrieved 13 October 2019.
- ↑ "Velcade". European Medicines Agency (EMA). 17 September 2018. Retrieved 13 October 2019.
- ↑ Bonvini P, Zorzi E, Basso G, Rosolen A. Bortezomib-mediated 26S proteasome inhibition causes cell-cycle arrest and induces apoptosis in CD-30+ anaplastic large cell lymphoma. Leukemia. 2007 Apr;21(4):838-42. PMID:17268529 doi:10.1038/sj.leu.2404528
- ↑ Gelman JS, Sironi J, Berezniuk I, Dasgupta S, Castro LM, Gozzo FC, Ferro ES, Fricker LD. Alterations of the intracellular peptidome in response to the proteasome inhibitor bortezomib. PLoS One. 2013;8(1):e53263. PMID:23308178 doi:10.1371/journal.pone.0053263
