甲基氨酸与人类关键核酸载体的体外相互作用
Carolina Säll1, Gábor Koncsos2, Anna Klukovits2
1Development ADME, Novo Nordisk A/S, Måløv, Denmark.
Journal of pharmaceutical sciences
|June 26, 2023
概括
酸氨酸是状细胞病 (SCD) 的NDec的一个组成部分,不抑制关键的核酸转运体. 氨酸被CNT3活跃运输,这表明可以与相关药物安全地同时使用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物新陈代谢 药物新陈代谢
- 遗传学 遗传学 是一个
背景情况:
- NDec是一种口服配合的迪西他和四氨酸,正在为状细胞疾病 (SCD) 进行临床开发.
- 了解NDec组件与核酸载体的相互作用对于预测药物相互作用和确保患者安全至关重要.
研究的目的:
- 调查四氨酸是否抑制或是度 (CNT1-3) 和平衡 (ENT1-2) 核酸转运体的基质.
- 在状细胞病患者中评估NDec和其他影响这些载体的药物之间的药物相互作用的潜力.
主要方法:
- 使用的麦丁 - 达比犬II (MDCKII) 细胞过度表达人 CNT1, CNT2, CNT3, ENT1 和 ENT2 载体.
- 使用尿素和腺作为基质进行了核酸转运体抑制试验.
- 进行了四氨酸氨基酸积累试验,以确定转运器介导的吸收,并描述CNT3.3的动力参数 (Km,Vmax).
主要成果:
- 在测试度 (25和250微米) 的情况下,四氨氨酸并没有抑制CNT或ENT介导的尿素/腺素运输.
- 在CNT3表达细胞中观察到四氨酸积,估计的动力参数 (Km = 3,140 μM,Vmax = 1,600 pmol/mg蛋白/分钟).
- 在ENT2表达细胞中没有检测到显著的四氨酸积.
结论:
- 甲基氨酸不会显著影响CNT1,CNT2,ENT1或ENT2输送器的功能.
- 氨酸被CNT3活跃运输,这种载体通常不是常见的状细胞疾病药物的目标.
- 这些发现表明,NDec可能可以安全地与具有研究核酸转运物的基质或抑制剂的药物同时使用.
关键词:
吸收,分布,新陈代谢和分泌 (ADME) 的情况活动运输 活动运输清除许可证的情况毒品运输是毒品的运输.药物相互作用 药物相互作用方便运输的交通工具.在体外模型模型.的细胞MDCK细胞.核酸转运器 核酸转运器 核酸转运器药理动力学 药理动力学更多相关视频
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