2. Academic Validation
  3. Chip-DSF: A rapid screening strategy for drug protein targets

Chip-DSF: A rapid screening strategy for drug protein targets

  • Pharmacol Res. 2022 Aug;182:106346. doi: 10.1016/j.phrs.2022.106346.
Zhao Cui 1,  Peng Chen 2,  Caifeng Li 3,  Shiwen Deng 4,  Hongjun Yang 5
Affiliations

Affiliations

  • 1 Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 2 Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; Robot Intelligent Laboratory of Traditional Chinese Medicine, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China. Electronic address: [email protected].
  • 3 Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China; Robot Intelligent Laboratory of Traditional Chinese Medicine, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
  • 4 Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • 5 Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address: [email protected].
PMID: 35809766 DOI: 10.1016/j.phrs.2022.106346
Abstract

Identification of the drug target of lead compounds is an important means for rapid and efficient drug discovery. Protein chips are a high-throughput protein function analysis technology that has been widely used in screening drug protein targets in recent years. However, the verification of the results after high-throughput protein chip screening is still cumbersome. Based on our mature protein chip preparation platform, we prepared a protein chip containing 150 important high-frequency protein targets and used Antibodies to prove the availability of the protein chip. To improve the accuracy of target screening, we combined the label-free differential scanning fluorimetry (DSF) with the protein chip, proposing the Chip-DSF strategy. Subsequently, we tested the method with small molecular ginsenoside-Rg2 (Rg2). The Chip-DSF strategy was used to successfully screen the potential target protein KRAS(G12C) of Rg2. Consistently, we found that Rg2 could inhibit NCI-H23 cell proliferation by inducing cell cycle arrest. Also, we found that Rg2 could reduce the amount of KRAS protein and inhibit the phosphorylation of KRAS downstream key signaling protein ERK1, RPS6, and P70S6K in NCI-H23 cells. Collectively, our Chip-DSF strategy could achieve rapid target verification which improved the accuracy and efficiency of target screening of protein chips.

Keywords

Differential scanning fluorimetry; Drug discovery; Protein chip; Protein target; Target identification.

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