人类CYP2C9有机杀虫剂和神经毒剂替代物的新陈代谢
Pratik Shriwas1, Abigail M Noonchester2, Andre Revnew1
1Division of Medical Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Journal of xenobiotics
|January 21, 2026
概括
酶CYP2C9代谢有机 (OP) 农药,将产物转化为氧子. 许多OP化合物抑制CYP2C9活性,AI/ML模型有可能预测OP代谢.
科学领域:
- 生物化学 生物化学
- 酶学 是一种酶学.
- 毒理学 毒理学 毒理学
背景情况:
- 细胞染色体P450酶,特别是CYP2C9,对于药物代谢至关重要,并充当天然生物清除剂.
- 以前的研究表明,CYP2C9可以将某些有机 (OP) 农药的 (P=S) 转化为 (P=O) 形式.
研究的目的:
- 调查CYP2C9对更广泛的OP化合物的代谢能力.
- 评估各种OP化合物对CYP2C9的时间依赖性抑制.
- 探索分子对接结合能和CYP2C9-介导的OP代谢之间的相关性.
主要方法:
- 液体染色学-并联质谱学 (LC-MS/MS) 用于研究由CYP2C9.9引起的OP化合物代谢.
- 使用pFluor50化试验来确定依赖于时间的CYP2C9.9抑制.
- 使用CYP2C9的晶体结构进行了分子对接模拟 (PDB ID: 1OG5).
主要成果:
- 而CYP2C9则表现出一种更喜欢代谢子形式而不是OP化合物的氧子形式的偏好.
- 许多经过测试的OP化合物表现出对CYP2C9活性的时间依赖抑制.
- 在OP化合物的计算结合能和CYP2C9代谢之间观察到中度正相关性 (R = 0.59).
结论:
- CYP2C9在各种OP化合物的新陈代谢中发挥作用,对原产品有偏好.
- OP化合物可以以时间依赖的方式抑制CYP2C9活性,这表明潜在的毒理相互作用.
- 这些体外发现为开发AI/ML模型提供了基础,以预测OP化合物代谢和毒性,包括化学战剂.
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