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Your search keyword '"Chen, Zhe-Sheng"' showing total 22 results
Start Over Author "Chen, Zhe-Sheng" Journal biochemical pharmacology
22 results on '"Chen, Zhe-Sheng"'

21. Selective reversal of BCRP-mediated MDR by VEGFR-2 inhibitor ZM323881

Author

Zhang, Yun-Kai, primary, Zhang, Xiao-Yu, additional, Zhang, Guan-Nan, additional, Wang, Yi-Jun, additional, Xu, Huizhong, additional, Zhang, Dongmei, additional, Shukla, Suneet, additional, Liu, Lili, additional, Yang, Dong-Hua, additional, Ambudkar, Suresh V., additional, and Chen, Zhe-Sheng, additional

Published
2017
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22. Nilotinib (AMN107, Tasigna®) reverses multidrug resistance by inhibiting the activity of the ABCB1/Pgp and ABCG2/BCRP/MXR transporters

Author

Tiwari, Amit K., Sodani, Kamlesh, Wang, Si-Rong, Kuang, Ye-Hong, Ashby, Charles R., Chen, Xiang, and Chen, Zhe-Sheng

Subjects
*MULTIDRUG resistance, *PROTEIN-tyrosine kinase inhibitors, *MYELOID leukemia, *ATP-binding cassette transporters, *CANCER chemotherapy, *CANCER relapse, *GENE expression
Abstract

Abstract: Nilotinib, a BCR-Abl tyrosine kinase inhibitor (TKI), was developed to surmount resistance or intolerance to imatinib in patients with Philadelphia positive chronic myelogenous leukemia. Recently, it was shown that several human multidrug resistance (MDR) ATP-binding cassette (ABC) proteins could be modulated by specific TKIs. MDR can produce cancer chemotherapy failure, typically due to overexpression of ABC transporters, which are involved in the extrusion of therapeutic drugs. Here, we report for the first time that nilotinib potentiates the cytotoxicity of widely used therapeutic substrates of ABCG2, such as mitoxantrone, doxorubicin, and ABCB1 substrates including colchicine, vincristine, and paclitaxel. Nilotinib also significantly enhances the accumulation of paclitaxel in cell lines overexpressing ABCB1. Similarly, nilotinib significantly increases the intracellular accumulation of mitoxantrone in cells transfected with ABCG2. Furthermore, nilotinib produces a concentration-dependent inhibition of the ABCG2-mediated transport of methotrexate (MTX), as well as E217βG a physiological substrate of ABCG2. Uptake studies in membrane vesicles overexpressing ABCG2 have indicated that nilotinib inhibits ABCG2 similar to other established TKIs as well as fumitremorgin C. Nilotinib is a potent competitive inhibitor of MTX transport by ABCG2 with a K i value of 0.69±0.083μM as demonstrated by kinetic analysis of nilotinib. Overall, our results indicate that nilotinib could reverse ABCB1- and ABCG2-mediated MDR by blocking the efflux function of these transporters. These findings may be used to guide the design of present and future clinical trials with nilotinib, elucidating potential pharmacokinetic interactions. Also, these findings may be useful in clinical practice for cancer combination therapy with nilotinib. [Copyright &y& Elsevier]

Published
2009
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