[Proteasome inhibitors in cancer therapy].

Abstract

Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238), delanzomib (CEP-18770), oprozomib (ONX0912/PR-047) and marizomib (NPI-0052).

• Authors: Wioletta Romaniuk, Agnieszka Ewa Ołdziej, Justyna Zińczuk, Janusz Kłoczko
• Journal: Postepy higieny i medycyny doswiadczalnej (Online) (Postepy Hig Med Dosw (Online)) Vol. 69 Pg. 1443-50 (Dec 31 2015) ISSN: 1732-2693 [Electronic] Poland
• Vernacular Title: Inhibitory proteasomów w terapii onkologicznej.
• PMID: 27259216 (Publication Type: Journal Article, Review)

Chemical References

• 3-methoxy-2-(3-methoxy-2-((2-methyl-1,3-thiazol-5-yl)formamido)propanamido)-N-(1-(2-methyloxiran-2-yl)-1-oxo-3-phenylpropan-2-yl)propanamide
• Antineoplastic Agents
• Boronic Acids
• Dipeptides
• Lactones
• Oligopeptides
• Proteasome Inhibitors
• Pyrroles
• Thiazoles
• Threonine
• Bortezomib
• delanzomib
• marizomib
• carfilzomib
• Caspases
• Proteasome Endopeptidase Complex

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Boronic Acids (therapeutic use)
• Bortezomib (therapeutic use)
• Caspases (metabolism)
• Dipeptides
• Humans
• Lactones (therapeutic use)
• Multiple Myeloma (drug therapy)
• Neoplasms (drug therapy)
• Oligopeptides (therapeutic use)
• Proteasome Endopeptidase Complex (metabolism)
• Proteasome Inhibitors (pharmacology, therapeutic use)
• Proteolysis
• Pyrroles (therapeutic use)
• Thiazoles
• Threonine (analogs & derivatives, therapeutic use)