Abstract 1010: New thiol-ω(γ-lactam amide) SAHA analogues as potent histone deacetylase (HDAC) inhibitors
| Autor: | Davide Vignola, Claudio Pisano, Mario B. Guglielmi, Gianfranco Battistuzzi, Marcella Barbarino, Loredana Vesci, Ferdinando Maria Milazzo, Walter Cabri, Giuseppe Giannini |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Cancer Research. 73:1010-1010 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/1538-7445.am2013-1010 |
| Popis: | Histone deacetylase inhibitors (HDACi) are one of the last frontiers in pharmaceutical research. Two HDACi are already part of armamentarium of the anticancer drugs of the oncologists: Vorinostat, Zolinza® (SAHA) and Romidepsin, Istodax® (depsipeptide; FK-228), both licensed by the FDA for the treatment of cutaneous T-cell lymphoma (CTCL). Beyond them, more than twenty new drugs are currently under pre-clinical and clinical investigation as single agent and in combination therapies against different cancers and in other several novel therapeutic indications. Mainly they are hydroxamic acids and benzamide derivatives; however none has emerged superior to SAHA in terms of potency. In our search, we have selected a new generation of HDACi: thiol-based SAHA bearing a lactam amide in ω-position. This new generation was highly competitive compared to competing drugs, displaying sub-micromolar to low nanomolar inhibitor activity on HDACs, being especially powerful on HDAC6 isoform. They exhibited higher anti-proliferative activity than SAHA on different human cell lines. In vivo they were orally administered and showed a higher potency than SAHA, with a negligible toxicity. The overall profile of this new class of HDAC inhibitors, including synthesis and a comprehensive pharmacological characterization, will be presented. These encouraging results prompted us to select a drug candidate which is currently in a phase of pre-clinical evaluation. Citation Format: Giuseppe Giannini, Gianfranco Battistuzzi, Davide Vignola, Loredana Vesci, Ferdinando Maria Milazzo, Mario Berardino Guglielmi, Marcella Barbarino, Claudio Pisano, Walter Cabri. New thiol-ω(γ-lactam amide) SAHA analogues as potent histone deacetylase (HDAC) inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1010. doi:10.1158/1538-7445.AM2013-1010 |
| Databáze: | OpenAIRE |
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