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首页> 外文期刊>The Journal of Antibiotics: An International Journal >Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma.
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Romidepsin (Istodax, NSC 630176, FR901228, FK228, depsipeptide): a natural product recently approved for cutaneous T-cell lymphoma.

机译:罗米地辛(Istodax,NSC 630176,FR901228,FK228,depsipeptide):一种天然产物,最近被批准用于皮肤T细胞淋巴瘤。

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摘要

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.
机译:Romidepsin(Istodax)是组蛋白脱乙酰基酶(HDACs)的选择性抑制剂,于2009年11月被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紫罗兰色杆菌的培养物中发现的,紫罗兰色杆菌是从日本土壤样品中分离出来的革兰氏阴性细菌。这种双环化合物起着前药的作用,谷胱甘肽吸收到细胞中后,其二硫键被谷胱甘肽还原,从而使游离硫醇基团能够与HDAC I和II类酶活性位点中的Zn离子相互作用。由于该化合物的合成复杂性,以及来自生产生物的低产量,因此寻求类似物以产生可合成获得的替代物。作为一种T细胞淋巴瘤药物,罗米地辛在几乎没有有效疗法的情况下可为疾病提供有价值的新疗法。

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