新型微管蛋白抑制剂YMR-65在Caco-2细胞单层模型中的吸收机制研究

doi:10.12092/j.issn.1009-2501.2018.09.003

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (9): 983-988.doi: 10.12092/j.issn.1009-2501.2018.09.003

新型微管蛋白抑制剂YMR-65在Caco-2细胞单层模型中的吸收机制研究

樊阿莉，薛思琪，魏加莉，李宁，赵娣，卢杨，陈西敬

中国药科大学，基础医学与临床药学学院，临床药物代谢动力学研究室，南京 211198，江苏

收稿日期:2018-05-14 修回日期:2018-06-11 出版日期:2018-09-26 发布日期:2018-09-26
通讯作者: 陈西敬，男，教授，博导，研究方向：药物代谢动力学。 Tel:025-86185379 E-mail:chenxj-lab@hotmail.com
作者简介:樊阿莉，女，研究生，研究方向：药物代谢动力学。 Tel:025-86185379 E-mail：wodejiaren08531@126.com
基金资助:
国家自然科学基金资助项目(81473272，81503148)；中央高校重点项目(2632017ZD02)

Absorption mechanism of a novel tubulin inhibitor,YMR-65, in Caco-2 cell model

Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing 211198, Jiangsu, China

Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, Nanjing 211198, Jiangsu, China

Received:2018-05-14 Revised:2018-06-11 Online:2018-09-26 Published:2018-09-26

摘要/Abstract

摘要：

目的: 研究新型微管蛋白抑制剂YMR-65在Caco-2单层细胞模型中摄取、转运机制，为新药研发提供思路与方法。方法: 建立Caco-2细胞模型，以Caco-2细胞内摄取量考察时间、浓度及温度对化合物YMR-65在Caco-2细胞中摄取的影响，以表观渗透系数(Papp)评价时间、浓度及P-糖蛋白(P-gp)抑制剂维拉帕米对转运的影响。结果: 在摄取模型中，化合物YMR-65在Caco-2细胞中以时间、浓度依赖性方式进行摄取且在测定浓度范围内无明显饱和，温度对化合物摄取无统计学差异；在转运模型中，化合物YMR-65在Caco-2细胞中转运呈现时间、浓度依赖性，且时间、浓度及P-gp抑制剂对化合物在Caco-2细胞中的顶侧及基底侧Papp无统计学差异。结论: 被动扩散是化合物YMR-65在Caco-2细胞模型中的主要摄取转运方式，化合物YMR-65可能不是P-gp的底物。

关键词: 新型微管蛋白抑制剂, YMR-65, Caco-2细胞

Abstract:

AIM: To study the uptake and transport characteristics of a novel tubulin inhibitor, YMR-65, in Caco-2 cells model and to provide ideas and methods for new drug development. METHODS: By establishing Caco-2 cell model, the effects of time, concentration and temperature on the uptake of YMR-65 were studied using intracellular uptake amount. Time, concentration or verapamil on its transport in Caco-2 cells were evaluated using apparent permeability coefficient (Papp). RESULTS:In Caco-2 uptake model, the cumulative amount of YMR-65 in Caco-2 cells increased in time- and concentration- manners without obvious saturation and it seemed that the uptake characteristics was unaffected by temperature. Time, concentrations or P-gp inhibitor showed no significant difference to the apparent permeability coefficient (Papp) in Caco-2 cells. CONCLUSION: YMR-65 is passively diffused into Caco-2 cells and it suggests that P-gp might not be involved in the intracellular transport of YMR-65 and it might not be the substrate of P-gp.

Key words: novel tubulin inhibitor, YMR-65, Caco-2 cells

中图分类号:

R965.2

樊阿莉，薛思琪，魏加莉，李宁，赵娣，卢杨，陈西敬. 新型微管蛋白抑制剂YMR-65在Caco-2细胞单层模型中的吸收机制研究[J]. 中国临床药理学与治疗学, 2018, 23(9): 983-988.

FAN Ali, XUE Siqi, WEI Jiali, LI Ning, ZHAO Di, LU Yang, CHEN Xijing. Absorption mechanism of a novel tubulin inhibitor,YMR-65, in Caco-2 cell model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(9): 983-988.

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新型微管蛋白抑制剂YMR-65在Caco-2细胞单层模型中的吸收机制研究

Absorption mechanism of a novel tubulin inhibitor,YMR-65, in Caco-2 cell model

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