Pasteur Institute-Cenci Bolognetti Foundation, Drug Chemistry and Technologies Department, University of Rome Sapienza, Piazzale Aldo Moro 5, Rome, Italy.
Epigenomics. 2010 Apr;2(2):307-24. doi: 10.2217/epi.10.7.
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.
琥珀酰亚胺基戊二酰胺酸（伏立诺他）是首个被应用于治疗皮肤 T 细胞淋巴瘤的组蛋白去乙酰化酶抑制剂（HDACi）。此后，许多属于短链脂肪酸、羟肟酸、环肽或苯甲酰胺类的 HDACi 已在 II 期或 III 期临床试验中（单独或联合）进行了研究，用于治疗多种肿瘤。此外，HDACi 可用于抗疟疾和抗真菌治疗，并可在潜伏的细胞储库中重新激活 HIV-1 的表达，这表明它们可与高效抗逆转录病毒疗法联合使用。此外，它们还在神经退行性疾病（如亨廷顿病、帕金森病和弗里德里希共济失调）中证明了其疗效。特别是，一类新的双苯胺类化合物表现出一种特殊的作用机制，对亨廷顿病和弗里德里希共济失调具有显著的治疗效果。此外，一些 Sirtuin 抑制剂在细胞试验和小鼠肿瘤模型中表现出抗增殖作用，因此表明这些化合物在癌症治疗中具有一定作用。此外，SIRT2 选择性抑制剂 AGK-2 已被报道对帕金森病具有保护作用，而白藜芦醇和其他 Sirtuin 激活剂可用于治疗阿尔茨海默病。
