Docking profiles for (+)-strebloside, a cytotoxic cardiac glycoside identified from Streblus asper, and some of its derivatives and Na⁺/K⁺-ATPase have been investigated. In addition, binding between (+)-strebloside and its aglycone, strophanthidin, and several of their other molecular targets, including FIH-1, HDAC, KEAP1 and MDM2 (negative regulators of Nrf2 and p53, respectively), NF-κB, and PI3K and Akt1, have been inspected and compared with those for digoxin and its aglycone, digoxigenin. The results showed that (+)-strebloside, digoxin, and their aglycones bind to KEAP1 and MDM2, while (+)-strebloside, strophanthidin, and digoxigenin dock to the active pocket of PI3K, and (+)-strebloside and digoxin interact with FIH-1. Thus, these cardiac glycosides could directly target HIF-1, Nrf2, and p53 protein–protein interactions, Na⁺/K⁺-ATPase, and PI3K to mediate their antitumor activity. Overall, (+)-strebloside seems more promising than digoxin for the development of potential anticancer agents.

中文翻译：

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(+)-Strebloside 及其衍生物与 Na+/K+-ATPase 和其他靶标的相互作用

(+)-strebloside 的对接图谱，一种从Streblus asper鉴定的细胞毒性强心苷，及其一些衍生物和 Na ⁺ /K ⁺-ATP酶已被研究。此外，(+)-strebloside 与其苷元、strophanthidin 和它们的一些其他分子靶标之间的结合，包括 FIH-1、HDAC、KEAP1 和 MDM2（分别为 Nrf2 和 p53 的负调节剂）、NF-κB 和PI3K 和 Akt1 已被检查并与地高辛及其苷元地高辛的比较。结果表明，(+)-strebloside、地高辛及其苷元与 KEAP1 和 MDM2 结合，而 (+)-strebloside、strophanthidin 和 digoxigenin 与 PI3K 的活性口袋结合，(+)-strebloside 和地高辛与FIH-1。因此，这些强心苷可以直接靶向 HIF-1、Nrf2 和 p53 蛋白质-蛋白质相互作用、Na ⁺ /K ⁺-ATPase 和 PI3K 介导它们的抗肿瘤活性。总体而言，(+)-strebloside 似乎比地高辛更有希望开发潜在的抗癌药物。