首批临床研究的口服D因子抑制剂用于补充介导疾病的治疗
Venkat R Gadhachanda1, Jason A Wiles1, Steven D Podos1
1Small Molecule Research, Alexion, AstraZeneca Rare Disease, 100 College St, New Haven, 06510, CT, USA.
Pharmaceutical research
|June 25, 2025
概括
研究人员发现了danicopan和vermicopan,它们是补充因子D (FD) 的小分子抑制剂,用于治疗补充因子介导的疾病,如阳性夜间血红蛋白尿 (PNH). 这些化合物表现出强烈的抑制作用和有利的临床用药动力学.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
背景情况:
- 补充因子D (FD) 对补充激活的替代途径 (AP) 是至关重要的.
- AP的失调与各种补充介导疾病有关,包括阳性夜间血红蛋白尿 (PNH).
研究的目的:
- 确定和开发FD的小分子抑制剂.
- 发现具有适用于补充介导疾病临床研究的特征的化合物.
主要方法:
- 合成和体外测试化合物的效力,选择性和代谢稳定性.
- 在体外药理学评估评估FD的抑制,补充途径和疾病模型.
- 在动物模型中进行体内药理动力学和药理动力学评估.
主要成果:
- 丹尼科潘和维米科潘被确定为临床候选药物,证明了FD和AP的强大和选择性抑制.
- 这两种化合物在PNH体外模型中表现出适合口服的药物动力学特征和疗效.
- 在动物研究中,与danicopan相比,Vermicopan在体外强度改善,清除率降低,生物可用性更高.
结论:
- 达尼科潘和维米科潘的临床前数据支持他们在补充介导疾病中的临床研究.
- 丹尼科潘已被批准作为PNH的辅助疗法,针对外血管血解.
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