摘要
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.
基金
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)
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)
Sanofi scholarship program.
