NADPHnet:a novel strategy to predict compounds for regulation of NADPH metabolism via network-based methods  

作　　者：Fei Pan Cheng-nuo Wang Zhuo-hang Yu Zeng-rui Wu Ze Wang Shang Lou Wei-hua Li Gui-xia Liu Ting Li Yu-zheng Zhao Yun Tang 

机构地区：[1]Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism,Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai,200237,China

出　　处：《Acta Pharmacologica Sinica》2024年第10期2199-2211,共13页中国药理学报（英文版）

基　　金：supported by the National Key Research and Development Program of China(Grant 2019YFA0904800);the National Natural Science Foundation of China(Grant U23A20530,82173746 and 82104066);the Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism(Shanghai Municipal Education Commission).

摘　　要：Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies.However,the complex nature of NADPH metabolism poses challenges in achieving this goal.In this study,we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods.Different from traditional approaches only focusing on one single protein,NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view.Specifically,NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods,and characterized the impact of natural products on NADPH metabolism using a combined score,NADPH-Score.NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set.This approach was further employed along with molecular docking to identify 27 compounds from a natural product library,6 of which exhibited concentration-dependent changes of cellular NADPH level within 100μM,with Oxyberberine showing promising effects even at 10μM.Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer.Overall,NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.

关 键 词：NADPH metabolism network-based inference natural product computational prediction 

分 类 号：R96[医药卫生—药理学]