A proteomic landscape of pharmacologic perturbations for functional relevance

Zhiwei Liu; Shangwen Jiang; Bingbing Hao; Shuyu Xie; Yingluo Liu; Yuqi Huang; Heng Xu; Cheng Luo; Min Huang; Minjia Tan; Jun-Yu Xu

doi:10.1016/j.jpha.2023.08.021

Volume 14 Issue 1

Jan. 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(1): 128-139

Zhiwei Liu, Shangwen Jiang, Bingbing Hao, Shuyu Xie, Yingluo Liu, Yuqi Huang, Heng Xu, Cheng Luo, Min Huang, Minjia Tan, Jun-Yu Xu. A proteomic landscape of pharmacologic perturbations for functional relevance[J]. Journal of Pharmaceutical Analysis, 2024, 14(1): 128-139. doi: 10.1016/j.jpha.2023.08.021

Citation:

Zhiwei Liu, Shangwen Jiang, Bingbing Hao, Shuyu Xie, Yingluo Liu, Yuqi Huang, Heng Xu, Cheng Luo, Min Huang, Minjia Tan, Jun-Yu Xu. A proteomic landscape of pharmacologic perturbations for functional relevance[J]. Journal of Pharmaceutical Analysis, 2024, 14(1): 128-139. doi: 10.1016/j.jpha.2023.08.021

Citation:

Zhiwei Liu, Shangwen Jiang, Bingbing Hao, Shuyu Xie, Yingluo Liu, Yuqi Huang, Heng Xu, Cheng Luo, Min Huang, Minjia Tan, Jun-Yu Xu. A proteomic landscape of pharmacologic perturbations for functional relevance[J]. Journal of Pharmaceutical Analysis, 2024, 14(1): 128-139. doi: 10.1016/j.jpha.2023.08.021

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A proteomic landscape of pharmacologic perturbations for functional relevance

doi: 10.1016/j.jpha.2023.08.021

a. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China;
b. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China;
c. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, Guangdong, 528400, China;
d. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210023, China

Funds:

This work was supported by the Natural Science Foundation of China (Grant Nos.: 22225702 and 32322048), the National Key R&D Program of China (Grant No.: 2020YFE0202200), the Shanghai Academic/Technology Research Leader Program, China (Grant No.: 22XD1420900), Guangdong High-level New R&D Institute, China (Grant No.:2019B090904008), Guangdong High-level Innovative Research Institute, China (Grant No.:2021B0909050003), the Shanghai Rising-Star Program, China (Grant No.: 22QA1411100), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (Grant No.: 2021276), the Young Elite Scientists Sponsorship Program by China Association for Science and Technology, China (Grant No.: 2022QNRC001), and the open fund of State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, China (Grant No.: KF-202201). We also thank the support of the Innovative Research Team of High-Level Local Universities in Shanghai, China (Grant No.: SHSMU-ZDCX20212700) and Sanofi scholarship program.

Received Date: May 20, 2023
Accepted Date: Aug. 29, 2023
Rev Recd Date: Aug. 11, 2023
Publish Date: Aug. 31, 2023

Abstract

Abstract

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.
- Proteomics,
- Drug,
- Perturbation,
- Drug target,
- Drug combination

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References(62)

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