Pharmacodynamic and pharmacokinetic characteristics of YMR-65, a tubulin inhibitor, in tumor-bearing mice

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Ali FanXijing Chen

Abstract

YMR-65​, 5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3-methoxyphenyl)-4, 5-dihydro-1H-pyrazole-1-carboxamide, is a potential tubulin inhibitor exhibiting good anticancer activity. In our study, we illustrated the biological activities in HepG2 cells and the pharmacodynamic and pharmacokinetic profiles were evaluated in murine H22 hepatoma-bearing mice. Molecular docking assay and colchicine competition assay indicated that YMR-65 could bind tightly to the colchicine binding site of tubulin. Further investigation demonstrated that YMR-65 arrested cells in the G2/M phase of cell cycle and induced apoptosis in HepG2 cells. Compared with control group, the tumor growth inhibition determined by final relative volume of tumor/the initial tumor volume were 32.57%, 24.00% and 34.95%, respectively, for YMR-65 (10 mg/kg), YMR-65 (20 mg/kg) and CA4P (10 m/kg) groups. Besides there were no obvious body change or tissue damage (enhanced by histopathology study). YMR-65 administration at 10 and 20 mg/kg in H22 tumor-bearing mice resulted in 1.87- and 1.80-fold longer half time (t1/2) and 0.36- and 0.78-fold lower area under concentration-time curve (AUC0-∞) in plasma in contrast with normal mice at 10 mg/kg. Furthermore, YMR-65 showed a wide distr...Continue Reading

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Citations

Aug 6, 2020·International Journal of Molecular Sciences·Dimitris Matiadis, Marina Sagnou
Dec 24, 2018·European Journal of Medicinal Chemistry·Ya-Liang ZhangHai-Liang Zhu
Aug 20, 2019·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Rasha Mohamed HassanMohamed Nabil Aboul-Enein
Jan 21, 2021·Bioorganic & Medicinal Chemistry Letters·Ting ZhuSai-Yang Zhang
Sep 10, 2020·Current Topics in Medicinal Chemistry·Feng SongMeng Zhou

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