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.

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.

Abcb1a/1b-mediated transport of daraxonrasib across the BBB was validated by oral co-administration of the ABCB1/ABCG2 inhibitor elacridar, resulting in 20-fold increased brain penetration in wild-type mice (P < 0.01). ABCB1 function could limit brain penetration and possibly efficacy of daraxonrasib against brain metastases. Collectively, these preclinical findings may help in optimizing the application of daraxonrasib in clinical settings.

OB-001, a KinetiSol® amorphous solid dispersion formulation of elacridar, was developed to overcome poor bioavailability of crystalline elacridar and evaluated as a strategy to enhance osimertinib brain delivery. OB-001 selectively boosts osimertinib brain exposure while sparing systemic PK. These preclinical data support further evaluation of OB-001 as a strategy to enhance CNS efficacy of osimertinib in EGFR-mutant NSCLC.

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.

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.

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.

P=N/A, N=100, Not yet recruiting, Assiut University

This study describes, for the first time in literature, a suitable approach to develop co-encapsulated magnetic nanoparticles based on fluorescent biotinylated N-palmitoyl chitosan, hydrophobic magnetite, Docetaxel and Verapamil. No significant toxicity was observed for magnetic nanoparticles in the rats. Overall, these findings suggest that the developed magnetic nanoplatforms represents a promising candidate for breast cancer applications and merits further in vivo investigation needed to elucidate the action mechanism of encapsulated therapeutics and their pharmacologic activity.

Among the tested compounds, Tetrandrine, Dauricine, and Olmutinib exhibited robust binding affinities across both wild-type and mutant EGFR configurations, highlighting their potential as effective inhibitors. The integrated approach of combining molecular docking using CB-dock2, ADMET profiling, and Lipinski's rule of five provides a robust framework for preliminary drug candidate screening, potentially accelerating the development of more precise and effective EGFR-targeted therapies. The findings contribute to the growing body of research exploring alternative and more nuanced strategies for inhibiting EGFR-driven oncogenic mechanisms, highlighting the importance of computational methods in identifying novel molecular targets with improved specificity and reduced side effects.

P1/2, N=24, Recruiting, Amsterdam UMC | Not yet recruiting --> Recruiting