Virtual Screening of Traditional Chinese Medicine Natural Product Inhibitors Targeting AQP1 for Bladder Cancer

Bladder cancer (BCa) is the most common and representative type of adult urinary tract urothelial cancer, characterized by high incidence and mortality rates. It has become a major disease threatening public health, highlighting the urgent need for the development of comprehensive treatment strategies, including traditional Chinese medicine, immunotherapy, and genetic diagnostics. Aquaporin-1 (AQP1), a water channel protein, mediates water transport across the cell membrane. Recent studies have shown that aquaporins are involved in the development and progression of malignant tumors. In particular, AQP1 plays a significant role in the pathogenesis of bladder cancer and may serve as a potential target for novel drug development. Natural products, owing to their structural diversity, represent a valuable reservoir of lead compounds for drug discovery.

In this study, we employed molecular docking and molecular dynamics simulations to screen a library of 2000 traditional Chinese medicine natural compounds for potential activity against the target protein AQP1. The final analysis identified 17 compounds with high binding affinity for the active site of AQP1, indicating their potential as candidate inhibitors. Among these, compounds 8 (Clematignoside), 10 (Ginsenoside Rb2), and 15 (Tannic acid) demonstrated particularly strong binding affinity and complex stability in molecular dynamics simulations.

These findings provide a valuable foundation for the rational design of AQP1-targeted pharmacophores and suggest promising candidates for the future development of clinical drugs for the treatment of bladder cancer. The top-ranked compounds, especially compounds 10 and 15, warrant further experimental investigation.