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4 HDAC抑制剂的分类1999年,Sloan-Kettering等取得了HDLP与SAHA及HDLP与TSA结合的晶体结构,并以此结构构建HDAC抑制剂的药效团模型(图1)。HDAC抑制剂一般包括锌离子结合区,连接区和表面识别区三部分。其中金属离子结合区能很好的与活性部位的锌离子直接作用,与组氨酸和酪氨酸等残基形成氢键。锌离子结合区是能与锌离子配位的基团,通常为羟肟酸、巯基、环氧酮或亲电酮类。抑制剂与锌
4 Classification of HDAC Inhibitors In 1999, Sloan-Kettering et al. Obtained the crystal structure of HDLP and SAHA combined with HDLP and TSA. Based on this structure, a pharmacophore model of HDAC inhibitor was constructed (Fig. 1). HDAC inhibitors generally include a zinc ion binding region, a linker region, and a surface recognition region. The metal ion binding region can directly interact with the zinc ion in the active site and form hydrogen bonds with residues such as histidine and tyrosine. Zinc ion binding sites are groups that coordinate to zinc ions and are typically hydroxamic acids, mercapto, epoxyketones, or electrophilic ketones. Inhibitors and zinc