深入了解有机功能群的基于结构的反应性代谢物形成过程
Chunyong He1, Yuchang Mao1, Hong Wan2
1Department of DMPK/Tox, Shanghai Hengrui Pharmaceutical Co. Ltd., Shanghai, China.
Drug metabolism reviews
|February 26, 2025
概括
反应性代谢物导致药物诱导性肝损伤 (DILI),导致药物戒断. 了解有机功能组生物激活有助于药物化学家设计更安全的候选药物,降低DILI风险.
科学领域:
- 药用化学 医学化学
- 药物新陈代谢 药物新陈代谢
- 毒理学 毒理学 毒理学
背景情况:
- 药物诱导的奇异性肝损伤 (DILI) 是药物消耗的主要原因之一.
- 反应性代谢物形成是DILI的关键贡献者.
- 在药物开发过程中,识别和减轻反应性代谢物至关重要.
研究的目的:
- 分析有机功能组的生物激活机制.
- 为基于结构的反应性代谢物形成提供见解.
- 协助设计更安全的药物候选药物,以提高安全性.
主要方法:
- 关于活性代谢物形成的文献综述.
- 对GSH/蓝色捕捉和细胞染色体P450无活化研究的分析.
- 对DILI.的结构-活动关系的检查.
主要成果:
- 在反应性代谢物形成中涉及的常见有机功能组被确定.
- 生物激活途径和有害影响详细说明,并附示例.
- 影响DILI风险的因素,如剂量和服用途径,讨论.
结论:
- 对功能组生物激活的深入理解对于合理的药物设计至关重要.
- 缓解反应性代谢物形成可以显著提高药物安全性.
- 这一审查有助于药物化学家和代谢科学家开发成功的候选药物.
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