Abstract
Aberrations in the Ubiquitin-Proteasome System (UPS) have been recently connected to the pathogenesis of several human protein degradation disorders (e.g., cancer and neurodegenerative diseases), so that proteasome is now considered an important _target for drug discovery. Small molecules able to inhibit and modulate UPS have been, in fact, described as novel tools for a new approach in anti-cancer therapy. In particular Proteasome Inhibitors (PIs), blocking activation of nuclear factor-kappa B (NF-kB), trigger a decreased cellular proliferation and angiogenic cytokine production, induce cell death and inhibit tumor cell adhesion to stroma. Furthermore, several studies have demonstrated that PIs potentiate the activity of other anti-cancer treatment, in part by down-regulating chemoresistance pathways. Therefore pharmacologic, preclinical, and clinical data suggested the use of PIs in anticancer strategies, for their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases. This review focuses on recent advances in the development of PIs anticancer agents highlighting both novel patented compounds and novel therapeutic protocol of intervention.
Keywords: Proteasome Inhibitors (PIs), protein degradation disorders, cancer
Recent Patents on Anti-Cancer Drug Discovery
Title: Proteasome Inhibitors Therapeutic Strategies for Cancer
Volume: 4 Issue: 1
Author(s): Annamaria D'Alessandro, Luisa Pieroni, Maurizio Ronci, Simona D'Aguanno, Giorgio Federici and Andrea Urbani
Affiliation:
Keywords: Proteasome Inhibitors (PIs), protein degradation disorders, cancer
Abstract: Aberrations in the Ubiquitin-Proteasome System (UPS) have been recently connected to the pathogenesis of several human protein degradation disorders (e.g., cancer and neurodegenerative diseases), so that proteasome is now considered an important _target for drug discovery. Small molecules able to inhibit and modulate UPS have been, in fact, described as novel tools for a new approach in anti-cancer therapy. In particular Proteasome Inhibitors (PIs), blocking activation of nuclear factor-kappa B (NF-kB), trigger a decreased cellular proliferation and angiogenic cytokine production, induce cell death and inhibit tumor cell adhesion to stroma. Furthermore, several studies have demonstrated that PIs potentiate the activity of other anti-cancer treatment, in part by down-regulating chemoresistance pathways. Therefore pharmacologic, preclinical, and clinical data suggested the use of PIs in anticancer strategies, for their potential therapeutic relevance in the treatment of cancer and inflammatory-related diseases. This review focuses on recent advances in the development of PIs anticancer agents highlighting both novel patented compounds and novel therapeutic protocol of intervention.
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D'Alessandro Annamaria, Pieroni Luisa, Ronci Maurizio, D'Aguanno Simona, Federici Giorgio and Urbani Andrea, Proteasome Inhibitors Therapeutic Strategies for Cancer, Recent Patents on Anti-Cancer Drug Discovery 2009; 4 (1) . https://dx.doi.org/10.2174/157489209787002452
DOI https://dx.doi.org/10.2174/157489209787002452 |
Print ISSN 1574-8928 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3970 |
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