P3, N=130, Completed, Milestone Pharmaceuticals Inc. | Enrolling by invitation --> Completed

P=N/A, N=43, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

P4, N=2, Terminated, Columbia University | N=104 --> 2 | Trial completion date: Dec 2027 --> Aug 2025 | Recruiting --> Terminated | Trial primary completion date: Dec 2026 --> Aug 2025; Principal investigator left the institution

Fangchinoline, a bisbenzylisoquinoline alkaloid derived from Stephaniae tetrandrine, is known for its antioxidant and anticancer potential...Fangchinoline exhibits promising anticancer activity by targeting ERBB2 and modulating critical oncogenic and apoptotic pathways. Its ability to upregulate p53 and ROS while suppressing PI3K/Akt/mTOR signalling suggests its strong potential as a HER-2-targeted therapeutic agent.

Mechanistically, calcium channel acts as the mechano-sensor to initiate the SS-ROS cascade, with calcium channel blockers Mibefradil and Nifedipine effectively weakening SS-ROS-induced invasiveness. Following ROS elevation, the downstream activation of p38-ELK1-cFOS and JNK-cJUN pathways subsequently increase the expression of malignancy-related genes. This metastasis-promoting SS-calcium channel-ROS-FOS axis provides new insights for combating metastatic progression in breast cancer.

Using molecular dynamics and in vitro models, we demonstrate that the FDA-approved calcium channel blocker nifedipine binds stably to Cav1.2 and suppresses tumor cell growth more effectively than cisplatin. Identification of a tumor biomarker that can be used for screening, diagnosis, and monitoring is critical for improving clinical outcome. Our findings demonstrate that CACNA1C is a viable diagnostic marker for HGSOC and that its blockade with CCBs reduces tumor progression, highlighting their therapeutic potential.

Inhibition of autophagic flux using Bafilomycin A1 or Tetrandrine rescued cells from apoptosis, confirming that excessive autophagy is the direct cause of cell death...The combination of APO-Cyt C and SA triggers apoptosis by overwhelming the cell with excessive autophagic flux, driven by synergistic inhibition of the mTOR-TFEB axis. These findings highlight the therapeutic potential of modulating autophagy and suggest that combining mTOR inhibitors with lysosome-targeting agents like SA could be an effective anti-cancer strategy.

P3, N=857, Active, not recruiting, Assistance Publique - Hôpitaux de Paris | Recruiting --> Active, not recruiting

P=N/A, N=264, Completed, Assiut University | Recruiting --> Completed | Trial completion date: Feb 2026 --> Sep 2025 | Trial primary completion date: Nov 2025 --> Jul 2025

Celastrol reduced P-gp expression and increased intracellular drug accumulation, comparable to verapamil. Celastrol synergizes with 5-FU to overcome chemoresistance in osteosarcoma by enhancing p53-mediated and -independent apoptosis and inhibiting P-gp-mediated drug efflux. These findings suggest a promising low-toxicity therapeutic strategy, warranting further in vivo and clinical investigations.

P1, N=74, Recruiting, University of Alabama at Birmingham | Trial completion date: Jun 2026 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026

P4, N=110, Recruiting, Western Galilee Hospital-Nahariya