Bortezomib
From Proteopedia
(Difference between revisions)
| (13 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | <StructureSection load='' size='340' side='right' caption='Caption for this structure' scene=''> | + | <StructureSection load='' size='340' side='right' caption='Caption for this structure' scene='10/1022872/Cv/1'> |
| - | Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma.[ | + | Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma.<ref name="a2">[https://www.drugs.com/monograph/bortezomib.html "Bortezomib Monograph for Professionals".] Drugs.com. Retrieved 13 October 2019.</ref> This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications.<ref name="a3">[https://www.ema.europa.eu/en/medicines/human/EPAR/velcade "Velcade".] European Medicines Agency (EMA). 17 September 2018. Retrieved 13 October 2019.</ref> See also [https://en.wikipedia.org/wiki/Bortezomib Bortezomib]. |
| + | |||
| + | Bortezomib is an N-protected dipeptide and can be written as <scene name='10/1022872/Cv/2'>Pyz-Phe-boroLeu</scene>, which stands for <scene name='10/1022872/Cv/3'>pyrazinoic acid, phenylalanine and Leucine with a boronic acid</scene> instead of a carboxylic acid. | ||
| + | |||
| + | The boron atom in bortezomib binds the catalytic site of the 20S proteasome<ref name="a15">PMID:17268529</ref> with high affinity and specificity. | ||
| + | *<scene name='10/1022872/Cv/4'>20S proteasome</scene> ([[2f16]]). | ||
| + | *<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/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. | ||
| - | [[2f16]]. | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
| |||||||||||
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
