Compound 17 exhibited the strongest cytotoxic effect against HepG2 cells with an IC50 value of 2.09 μM and a satisfactory SI value of 11.5, which was 5.3- and 6.4-fold higher than the activity of parental tetrandrine and adriamycin, respectively. Moreover, it indicates a potent in vivo killing effect against liver cancers, orthotopically transplanted HCC in an AKT1-dependent manner, with a safety profile. Taken together, compound 17 shows therapeutic potential as a safe anticancer agent through apoptosis induction, worthy of further development.

P1/2, N=60, Recruiting, Mayo Clinic | Not yet recruiting --> Recruiting

P=N/A, N=20, Recruiting, University of Iowa | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

P3, N=600, Completed, Kafrelsheikh University | Recruiting --> Completed | Trial completion date: May 2025 --> Apr 2026 | Trial primary completion date: Apr 2025 --> Apr 2026

Compound 3 (3α-dihydrocadambine) effectively revealed strong vasodilatory activity with EC50 values of 2.4 μM and 2.1 μM, respectively, similar levels comparable to the positive control (verapamil)...Moreover, network pharmacology and molecular docking predicted compound 1 to correlate with the p53-Hippo-TGF-β antitumor signalling pathway and compound 3 with the cAMP/cGMP-PKG cardiovascular signalling pathway. This work provides preliminary experimental data for the development of potential lead compounds from U. gambir.

Bulk and single-cell transcriptomic analyses further revealed complement-associated activation, extracellular-matrix remodeling, and enrichment of antigen-presenting and inflammatory macrophage programs. Thus, TETNPs@Gel functions as an in situ nanovaccine rather than a conventional cytotoxic formulation, in which controlled tetrandrine release couples direct tumor-cell killing with vascular and immune re-education, offering a potentially generalizable platform for localized immunochemotherapy in solid tumors.

P2, N=136, Completed, Medical University of Graz | Active, not recruiting --> Completed

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.