华东理工大学唐赟等研究人员合作开发出通过基于网络的方法预测NADPH代谢调节化合物的新策略。相关论文于2024年6月20日在线发表于国际学术期刊《中国药理学报》。

研究人员提出了一种名为NADPHnet的新策略，通过基于网络的方法预测与NADPH代谢相关的关键蛋白和药物靶点相互作用。与传统的只关注单一蛋白质的方法不同，NADPHnet可以从全面的角度筛选调节NADPH代谢的化合物。具体来说，NADPHnet利用基于网络的方法确定了参与调控NADPH代谢的关键蛋白，并利用综合得分NADPH-Score表征了天然产物对NADPH代谢的影响。NADPHnet的适用范围更广，外部验证集的准确性也有所提高。

该方法与分子对接相结合，从天然产物库中鉴定出了27种化合物，其中6种在100 μM的浓度范围内表现出了细胞NADPH水平的浓度依赖性变化，而氧化小檗碱甚至在10μM的浓度范围内也表现出了良好的效果。氧化小檗碱的机理和病理分析表明，它具有影响糖尿病和癌症的潜在新机制。总之，NADPHnet为预测NADPH代谢调节提供了一种有前途的方法，并推动了复杂疾病的药物发现。

据悉，鉴定调节NADPH代谢的化合物对于了解复杂疾病和开发有效疗法至关重要。然而，NADPH代谢的复杂性给实现这一目标带来了挑战。

附：英文原文

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

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

Issue&Volume: 2024-06-20

Abstract: 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.

DOI: 10.1038/s41401-024-01324-6

Source: https://www.nature.com/articles/s41401-024-01324-6