Recently, the team of Ninghua Tan/Zhe Wang from the School of Traditional Chinese Medicine, together with the team of Yi Ma from the School of Engineering, published their latest research results “Identification of Novel Target DCTPP1 for Colorectal Cancer Therapy with the Natural Small-molecule Inhibitors Regulating Metabolic Reprogramming”. Li Feng, a postdoctoral fellow at the School of Traditional Chinese Medicine, and Xinjia Wang, a master's student, were the co-first authors, and China Pharmaceutical University was the sole correspondent.
Drugs derived from natural products have been widely used in the treatment of major diseases, such as malignant tumors, cardiovascular, cerebrovascular and metabolism-related diseases, etc., and the lack of new targets is one of the major reasons limiting the development of original drugs. The interaction of active natural products with intracellular target proteins is the basis for their efficacy, so the discovery of new clinically effective targets using active natural products is an effective strategy for original drug development. The team of Ninghua Tan/Zhe Wang has been working on the discovery and mechanism of action of active natural products from cyclic peptide-containing traditional Chinese medicines and their microbial resources. To address the above issues, the team has systematically carried out a series of work related to the “discovery of novel active natural products, investigation of target mechanism of action, and development of new target drug candidate molecules”, and has made a series of progress in the past five years. Eur. J. Med. Chem. 2024, 268, 116175; J. Agr. Food Chem. 2024, 72, 2598; J. Nat. Prod. 2023, 86, 1449/2019, 82, 1434; Phytochemistry 2023, 207, 113579/2022, 200, 113180/2020, 200, 113180/2020, 200, 113180/2020, 200, 113180/2020, 200, 113180/2020; J. Nat. , 200, 113180/2020, 179, 112505; J. Org. Chem. 2022, 87, 14058).
Cissus chinensis is a traditional Chinese medicine commonly used in China and has important medicinal value. The team comprehensively utilized OSMAC, metabolomics and molecular network visualization to isolate a series of terpene-nonadride heterodimers and their monomers from the endophytic fungi of Cynodon grandiflorum with novel backbones. Among them, the compound bipoterpride B has better ex vivo anticolorectal cancer (CRC) activity than the clinical first-line antitumor drugs 5-fluorouracil and cisplatin. Further, the team discovered potential targets of action of bipoterpride B based on DARTS and proteomics technologies, and found DCTPP1 to be a new target for the treatment of CRC using bioinformatics technologies, clinical samples, and so on, and also demonstrated that bipoterpride B could exert anticolorectal cancer activity by targeting DCTPP1. The above work covers the important process of Chinese medicinal chemistry/natural medicinal chemistry research, including chemical analysis, extraction and isolation, structural identification, activity screening, in vivo evaluation and target mechanism research, which enriches the structural diversity of natural products and provides new therapeutic targets for colorectal cancer, and also discovers the first anticolorectal cancer natural inhibitor targeting DCTPP1, which provides a potential candidate molecule for antitumor drug research. potential candidate molecules for anti-tumor drug research.
The above work was supported by the National Natural Science Foundation of China under the Supervisory and Youth Programs, the Basic Research Funds of the Central Universities, the “Double First Class” Program of China Pharmaceutical University, and the Excellence Postdoctoral Program of Jiangsu Province.
Original link: https://onlinelibrary.wiley.com/doi/abs/10.1002/ange.202402543
