Sura Madhu Babu, Zhou Yeting, Li Jijun, Cheng Yongxian
Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Marshall Laboratory of Biomedical Engineering, Institute for Inheritance-Based Innovation of Chinese Medicine, School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen 518060, China.
Acta Pharm Sin B. 2025 Jun;15(6):3181-3195. doi: 10.1016/j.apsb.2025.04.004. Epub 2025 Apr 8.
Chronic kidney disease (CKD) affects 8%-15% of the population globally and can cause renal failure, partly due to lack of effective treatments and drug targets. Three novel cembrane diterpenoids papyifurans A‒C (-), in particular of with an unprecedented trioxatetracyclo[10.2.1.1.1]heptadecane polyether scaffold, derived from resin, were found to effectively protect against renal fibrosis and . Their structures were fully characterized using a combination of spectroscopic, computational, modified Mosher's, and X-ray crystallographic analysis. In particular, we performed chemical proteomic analyses and found that Elongation factor 2 (EEF2) is the key target of compound for anti-renal fibrosis . Moreover, previous studies have linked EEF2 with lung fibrosis, while compound was found to inhibit the hallmarks of organ fibrosis Such effects were observed to decrease with the knock down of EEF2 , suggesting that EEF2 might be a universal drug target of organ fibrosis. Collectively, the present study demonstrated an example of identifying drug targets by using structurally novel natural products, which will be beneficial for developing therapeutic agents against organ fibrosis.
慢性肾脏病（CKD）影响着全球8%-15%的人口，并且可能导致肾衰竭，部分原因是缺乏有效的治疗方法和药物靶点。从树脂中分离出三种新型的贝壳杉烷二萜类化合物——纸呋喃A-C（-），特别是具有前所未有的三氧杂四环[10.2.1.1.1]十七烷聚醚骨架的化合物，被发现能有效预防肾纤维化。通过光谱分析、计算分析、改良的莫舍尔法以及X射线晶体学分析相结合的方法，对它们的结构进行了全面表征。特别是，我们进行了化学蛋白质组学分析，发现延伸因子2（EEF2）是化合物抗肾纤维化作用的关键靶点。此外，先前的研究已将EEF2与肺纤维化联系起来，而化合物被发现可抑制器官纤维化的特征。随着EEF2基因敲低，这些作用减弱，这表明EEF2可能是器官纤维化的通用药物靶点。总体而言，本研究展示了一个利用结构新颖的天然产物来鉴定药物靶点的实例，这将有助于开发针对器官纤维化的治疗药物。
