Affiliation:
1. Pasteur Institute – Cenci Bolognetti Foundation, Drug Chemistry and Technologies Department, University of Rome ‘Sapienza’, Piazzale Aldo Moro 5, 00185 Rome, Italy.
Abstract
Suberoylanilide hydroxamic acid (vorinostat) was the first of the histone deacetylase inhibitors (HDACi) to be entered as therapy for the treatment of cutaneous T-cell lymphoma. Since then, a number of HDACi belonging to the short-chain fatty acid, hydroxamate, cyclic peptide or benzamide classes have been investigated in Phase II or III clinical trials (alone or in combination) for the treatment of many kinds of tumors. In addition, HDACi can be useful in antimalarial and antifungal therapies, and can reactivate HIV-1 expression in latent cellular reservoirs, thus suggesting that they could be used in combination with highly active antiretroviral therapy. Moreover, they have also proved their efficacy in neurodegenerative diseases, such as Huntington’s disease, Parkinson’s disease and Friedreich’s ataxia. In particular, a new series of bis-anilides demonstrating a peculiar mechanism of action displayed highly beneficial effects against Huntington’s disease and Friedreich’s ataxia. In addition, a number of sirtuin inhibitors demonstrated antiproliferative effects in cell assays as well as in mouse tumor models, thus suggesting a role of such compounds in therapy against cancer. Furthermore, the SIRT2-selective AGK-2 has been reported to have protective effects against Parkinson’s disease, and resveratrol and other sirtuin activators can be useful for the treatment of Alzheimer’s disease.
Cited by
27 articles.
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