Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, NC 27402, USA.
J Antibiot (Tokyo). 2011 Aug;64(8):525-31. doi: 10.1038/ja.2011.35. Epub 2011 May 18.
Romidepsin (Istodax), a selective inhibitor of histone deacetylases (HDACs), was approved for the treatment of cutaneous T-cell lymphoma in November 2009 by the US Food and Drug Administration. This unique natural product was discovered from cultures of Chromobacterium violaceum, a Gram-negative bacterium isolated from a Japanese soil sample. This bicyclic compound acts as a prodrug, its disulfide bridge being reduced by glutathione on uptake into the cell, allowing the free thiol groups to interact with Zn ions in the active site of class I and II HDAC enzymes. Due to the synthetic complexity of the compound, as well as the low yield from the producing organism, analogs are sought to create synthetically accessible alternatives. As a T-cell lymphoma drug, romidepsin offers a valuable new treatment for diseases with few effective therapies.
罗米地辛（Istodax）是一种组蛋白去乙酰化酶（HDACs）的选择性抑制剂，于 2009 年 11 月获得美国食品和药物管理局批准用于治疗皮肤 T 细胞淋巴瘤。这种独特的天然产物是从 Chromobacterium violaceum 的培养物中发现的，Chromobacterium violaceum 是一种革兰氏阴性菌，从日本土壤样本中分离得到。这种双环化合物作为前药，其二硫键在摄取到细胞内时被谷胱甘肽还原，使游离巯基与 I 类和 II 类 HDAC 酶的活性位点中的 Zn 离子相互作用。由于该化合物的合成复杂性以及产生该化合物的生物体的产量低，因此正在寻找类似物以创造可合成获得的替代物。作为一种 T 细胞淋巴瘤药物，罗米地辛为治疗有效疗法很少的疾病提供了一种有价值的新治疗方法。
