In metabolic stability assays using human liver microsomes, AQQ6 exhibited relatively low intrinsic clearance (Clint) and an improved half-life (T1/2) compared to verapamil. However, pharmacokinetic studies in rats indicated poor oral bioavailability (%F = 4.2), likely due to extensive hepatic metabolism in rat liver microsomes. Molecular dynamics simulations targeting MAPK8, the protein likely involved in AQQ6 activity, were conducted to elucidate molecular-level binding interactions.

P4, N=60, Active, not recruiting, Centre Hospitalier Universitaire de Nice | Recruiting --> Active, not recruiting | Trial completion date: Mar 2025 --> Sep 2027 | Trial primary completion date: Mar 2025 --> Sep 2025

P3, N=850, Recruiting, Assistance Publique - Hôpitaux de Paris | Trial completion date: Nov 2030 --> Nov 2031 | Trial primary completion date: Nov 2025 --> Nov 2026

Three components (quercetin, oleic acid, tetrandrine) were highlighted as particularly effective...In conclusion, the therapeutic effect of the HL-RG combination against RCC is primarily mediated by its bioactive components, QUE, OA, and TET. These components regulate the HIF-1 signaling pathway, activating genes involved in the cellular response to hypoxia and modulating the expression of proteins that control glucose metabolism, cell proliferation, and angiogenesis.

Dapagliflozin and trimetazidine each attenuated diabetes- and doxorubicin-related hepatic injury through partly distinct mechanisms, with the combination providing additive but not consistently superior effects. These findings suggest a potential hepatoprotective role for both agents; however, the clinical implications remain uncertain and require confirmation in further mechanistic and translational studies.

P=N/A, N=184, Recruiting, Hillel Yaffe Medical Center

Cisplatin resistance is a major contributor to treatment failure in ovarian cancer (OC). Molecular dynamics simulations demonstrated that hesperidin, cissamine and tetrandrine exhibited strong binding affinities toward AURKA, vitamin D receptor, and TTK. Future studies are encouraged to focus on the experimental validation of these compounds and delve deeper into the possible mechanisms of drug resistance, aiming to improve their therapeutic effectiveness and real-world applicability.

MDR1 inhibitor verapamil and MDR1-targeted siRNA were used to evaluate the functional impact of LSR-induced MDR1. In contrast, knockout of LSR expression in MDA-MB-468 cells, which express higher levels of LSR, significantly sensitized the cells to doxorubicin-induced growth inhibition and apoptosis. Our data demonstrated that LSR overexpression promotes TNBC cell proliferation and invasion, and upregulation of MDR1 in these cells renders them resistant to doxorubicin, suggesting that targeting LSR could be a useful strategy to overcome chemoresistance in TNBC.

P=N/A, N=64, Not yet recruiting, Affiliated hangzhou first people's hospital, zhejiang university school of medicine; Hangzhou First People's Hospital

P=N/A, N=60, Not yet recruiting, The First Affiliated Hospital of Army Medical University (Southwest Hospital); The First Affiliated Hospital of Army Medical University (Southwest Hos

Among these, NR-CL was validated as a disulfidptosis desensitizer, while lomerizine and clioquinol were confirmed as sensitizers through gene expression predictive analyses and cellular functional validation. These findings lay a robust foundation for uncovering novel regulatory mechanisms of disulfidptosis and provide practical strategies for enhancing cancer chemotherapy through targeted interventions.

Verapamil assays confirmed reduced efflux liability for compounds 8 and 13. Compound 8 also showed a positive therapeutic index. These findings support rational design to mitigate efflux-mediated resistance.