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| 维生素D类药物及其类似物的研发进展 |
| Research and development of vitamin D and its synthetic analogs |
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| DOI：10.3969/j.issn.1006-7108.2021.06.026 |
| 中文关键词: 维生素D 骨化醇 维生素D受体 |
| 英文关键词:vitamin D calcidol vitamin D receptor (VDR) |
| 基金项目: |
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| 中文摘要: |
| 维生素D3对于预防骨骼疾病、肌肉无力、自身免疫性疾病以及某些类型的癌症是必不可少的。维生素D3通过其代谢产物1α,25-二羟基维生素D3 [1,25(OH)2D3]充当转录因子维生素D受体（VDR）的有效激动剂。因此维生素D直接影响众多基因组位点及其靶组织的染色质结构和基因调控。近年来单独或组合修饰1,25(OH)2D3的侧链、A环、三烯系统或C环以及非甾体模拟物，均获得了多种有效的VDR激动剂和拮抗剂。目前为止，近150个VDR配体与各种维生素D类似物结合体的晶体结构已被逐渐阐明，使得这些化合物的作用机理明确至分子水平。本文综述了过去10年、尤其是近5年提出的重要维生素D类似物以及从有关VDR蛋白的新结构信息中得出的化合物分子水平的作用机理。 |
| 英文摘要: |
| Vitamin D3 is essential for preventing bone diseases, muscle weakness, autoimmune diseases and some types of cancer. Vitamin D3 serves as a potent agonist of the transcription factor vitamin D receptor (VDR) through its metabolite 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. Therefore, vitamin D directly affects a number of genome sites, chromatin structures of targeted tissue and gene regulation. A variety of effective VDR agonists and certain antagonists have been obtained by solely and combinedly modifying the side chain of 1,25 (OH) 2D3, A ring, triene system or C ring, as well as nonsteroidal mimetics. Nearly 150 crystal structures of a VDR ligand-binding domain with various vitamin D compounds have been gradually illuminated, which allows a molecular understanding of their action mechanisms. This review discusses the most important vitamin D analogs presented in the past 10 years and molecular mechanisms derived from new structural information related to the VDR protein. |
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