Obtain Substance of Anti-glioblastoma from Erigeron breviscapus through Fragment-based Target Research (FBTR): An Efficient Strategy for Pharmacology Investigation and Optimization of Natural Products

Chunguo Wang; Jinli Shi; Qinling Rao; Bingqing Shen; Canyu Su; Heng Chen; Zhixing Huang; Shuwei Jiang; Rongge He; Luni Xu; Muxuan Li; Yonggang Liu; Tao Ma; Yantong Xu; Xinqi Deng

doi:10.1016/j.jpha.2025.101366

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Chunguo Wang, Jinli Shi, Qinling Rao, Bingqing Shen, Canyu Su, Heng Chen, Zhixing Huang, Shuwei Jiang, Rongge He, Luni Xu, Muxuan Li, Yonggang Liu, Tao Ma, Yantong Xu, Xinqi Deng. Obtain Substance of Anti-glioblastoma from Erigeron breviscapus through Fragment-based Target Research (FBTR): An Efficient Strategy for Pharmacology Investigation and Optimization of Natural Products[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101366

Citation:

Chunguo Wang, Jinli Shi, Qinling Rao, Bingqing Shen, Canyu Su, Heng Chen, Zhixing Huang, Shuwei Jiang, Rongge He, Luni Xu, Muxuan Li, Yonggang Liu, Tao Ma, Yantong Xu, Xinqi Deng. Obtain Substance of Anti-glioblastoma from Erigeron breviscapus through Fragment-based Target Research (FBTR): An Efficient Strategy for Pharmacology Investigation and Optimization of Natural Products[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101366

Citation:

Chunguo Wang, Jinli Shi, Qinling Rao, Bingqing Shen, Canyu Su, Heng Chen, Zhixing Huang, Shuwei Jiang, Rongge He, Luni Xu, Muxuan Li, Yonggang Liu, Tao Ma, Yantong Xu, Xinqi Deng. Obtain Substance of Anti-glioblastoma from Erigeron breviscapus through Fragment-based Target Research (FBTR): An Efficient Strategy for Pharmacology Investigation and Optimization of Natural Products[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101366

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Obtain Substance of Anti-glioblastoma from Erigeron breviscapus through Fragment-based Target Research (FBTR): An Efficient Strategy for Pharmacology Investigation and Optimization of Natural Products

doi: 10.1016/j.jpha.2025.101366

a. Beijing University of Chinese Medicine, Beijing, 102488, China;
b. Institute of Chinese materia medica China academy of Chinese medical sciences, Beijing, 100700, China

Funds:

This research was funded by the Natural Science Foundation of Beijing, China (Grant No.: 7244493), the National Natural Science Foundation of China (NSFC) (Grant Nos.: 82404932, 82374076, and 81703744), the NSFC Cultivating Project by Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China (Grant No.: ZXKT23003), Young Elite Cultivating Project by Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, China (Grant No.: ZZ17-YQ-023), the National Key R&

D Program of China (Grant No.: 2023YFC3504100), and the Research Project on Standardization of Experimental Techniques (Operating Procedures) in Beijing University of Chinese Medicine, China (Grant No.: 2023-syjs-01).

Received Date: Jan. 15, 2025
Accepted Date: Jun. 11, 2025
Rev Recd Date: Jun. 07, 2025
Available Online: Jun. 18, 2025

Abstract

Abstract

Natural products (NPs) make a major contribution to drug development, offering a huge molecule pool for drug leads. Nevertheless, the pharmaceutical industry and academy have declined their enthusiasm to NPs research since the great challenges in elucidating the complex component and intricate mechanism of NPs. Here, we introduce an efficient fragment-based target research (FBTR) approach for pharmacology study and optimization of NPs. Focusing on the core fragment within the molecules of NPs, we screen the outstanding activity that be triggered, and corresponding target. Finally, drug optimization was carried out around the molecules that obtaining the activity-related core fragment and verified both in vitro and in vivo. With this approach, we obtained an optimized NPs named Erigeron breviscapus polyphenols (EBP) with definite target. After optimization, Erigeron breviscapus polyphenols plus (EBPP) not only trigger immunogenic cell death (ICD) of glioblastoma (GBM) cells effectively by targeting to Cys105 amino acid site of Fas-associating protein with a novel death domain (FADD) protein, but also prolong the survival of GBM mice by an average of 17.6 days. Significantly, our investigation presents an approach for addressing challenges in NPs development and opening up new opportunities for drug discovery. Our findings demonstrate the utility of FBTR in exploring the function of NPs, revealing the target, and advancing drug optimization for stronger clinical translation.
- Fragment-based,
- Target,
- Drug optimization,
- Natural product

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References(56)

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