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The Effects of AT-533 and AT-533 gel on Liver Cytochrome P450 Enzymes in Rats

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Abstract

Background and Objectives

AT-533 is a novel heat shock protein 90 inhibitor, which exhibits various biological activities in vitro and in vivo. Cytochrome P450 (CYP) enzymes in the liver are involved in the biotransformation of drugs and considered to be essential indicators of liver toxicity. The aim of this study was to assess the effect of AT-533, either as active pharmaceutical ingredient or in gel form, on liver CYP enzymes.

Methods

The effect of AT-533 or AT-533 gel on rat liver cytochrome P450 enzymes, including CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, was analyzed using LC-MS/MS.

Results

AT-533 and AT-533 gel did not significantly increase or reduce the enzymatic activity of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 at any treatment dose.

Conclusions

AT-533 and AT-533 gel did not have any effect on CYP activity and may be considered safe for external use in gel form, as an alternative to conventional treatment.

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Acknowledgments

Yanting Wu would like to thank Mr. Hui Chen (Guangzhou University of Chinese Medicine) for the care and encouragement of the experimental progress.

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Author notes

  1. Yanting Wu and Menghe Li have contributed equally to this work and share first authorship

Authors and Affiliations

  1. Department of Cell Biology, College of Life Science and Technology, Jinan University, No. 601, Whampoa Road West, Guangzhou, 510632, People’s Republic of China

    Yanting Wu, Menghe Li, Tao Liu, Lishan Zhong, Chen Huang, Cuifang Ye, Qiuying Liu, Zhe Ren & Yifei Wang

  2. Department of Cell Biology, Guangdong Province Key Laboratory of Bioengineering Medicine, Guangdong Provincial Biotechnology Drug & Engineering Technology Research Center, National Engineering Research Center of Genetic Medicine, Guangzhou, People’s Republic of China

    Yanting Wu, Menghe Li, Tao Liu, Lishan Zhong, Chen Huang, Cuifang Ye, Qiuying Liu, Zhe Ren & Yifei Wang

  3. Department of Cell Biology, Guangzhou Jinan Biomedicine Research and Development Center Co. Ltd, Guangzhou, People’s Republic of China

    Yuying Guo & Yifei Wang

  4. Department of pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China

    Qiuying Liu

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  1. Yanting Wu
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Correspondence to Yifei Wang.

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Funding

This work was supported by the Guangzhou Major Program of the Industry-University-Research collaborative innovation (Grant numbers: 201604020178 & 201704030087).

Conflicts of interest

The authors declare no conflict of interest.

Ethics Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed and the study protocols were approved by The Institutional Animal Care and Use Committee of Jinan University Guangzhou, PR China.

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Authors' contributions

YW designed the study. YW, ML, YG, TL, LZ, CH, CY, QL and ZR performed the experiments. YW and ML performed the statistical analysis. YW drafted the manuscript. ML and YG made significant conceptual contributions to the manuscript. ZR and YW reviewed the final version of the paper. All the authors provided intellectual content and approved the final version of the manuscript.

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Wu, Y., Li, M., Guo, Y. et al. The Effects of AT-533 and AT-533 gel on Liver Cytochrome P450 Enzymes in Rats. Eur J Drug Metab Pharmacokinet 47, 345–352 (2022). https://doi.org/10.1007/s13318-022-00757-w

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