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Review Article

口服补体因子D抑制剂Danicopan（ACH-4471）的发现和开发

卷 27, 期 25, 2020

页: [4165 - 4180] 页: 16

弟呕挨: 10.2174/0929867326666191001130342

价格: $65

摘要

补体在我们对入侵微生物的天然免疫防御中起着至关重要的作用。但是，补体激活过度或宿主细胞激活控制不足可能与几种慢性疾病有关。补体因子D（CFD）是补体替代途径（AP）激活和扩增所必需的，是一种特异性丝氨酸蛋白酶，可裂解其独特的底物补体因子B（CFB），并与活化形式的补体成分3（ C3），以生成AP C3转化酶C3（H2O）Bb和C3bBb。这些转化酶是AP激活后引发效应子应答的重要组成部分，它们还为补体的经典途径（CP）和凝集素途径（LP）都提供了强大的扩增环。由于CP或LP的激活均不需要CFD，因此选择性CFD抑制为调节补体活性提供了一种有益的治疗方法，使CP和LP激活后保留了完整的效应子功能，因此比其他补体具有较低的细菌感染风险导向的方法。这篇综述提供了关于CFD抑制剂的最新信息，这些抑制剂已从显示出较差的选择性的不可逆小分子演变为显示出优异的选择性和效能的可逆小分子和单克隆抗体。可逆小分子抑制剂danicopan_（ACH-4471）最近作为有前途的治疗候选药物出现。介绍了其发现，临床前药理学，健康志愿者的1期临床研究以及阵发性夜间血红蛋白尿（PNH）患者的2期临床研究的概述。

关键词: 补体，替代途径，补体因子D，口服抑制剂，danicopan，_ACH-4471，PNH。

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