P=N/A, N=62, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P4, N=240, Not yet recruiting, China-Japan Friendship Hospital; ZHEJIANG JINHUA CONBA BIO-PHARM.CO.,LTD.

P=N/A, N=60, Recruiting, The First Affiliated Hospital of Army Medical University (Southwest Hospital); The First Affiliated Hospital of Army Medical University (Southwest Hos | Not yet recruiting --> Recruiting | Initiation date: Aug 2025 --> Nov 2025

Genetic silencing of ABCB1 or pharmacological inhibition with the specific P-glycoprotein modulator elacridar or tariquidar restored intracellular paclitaxel levels, as determined by UPLC-MS/MS, and synergistically decreased cell viability as observed in CCK-8 assay. These findings reveal that the ABCB1-mediated drug efflux is a crucial mechanism underlying paclitaxel resistance in NSCLC cells, with UPLC-MS/MS serving as a sensitive analytical method to detect paclitaxel concentration. Inhibition of ABCB1 is a promising therapeutic strategy to resensitize resistant tumor cells to paclitaxel.

These findings highlight tetrandrine's dual profile: a promising natural antiangiogenic agent with demonstrable efficacy, yet with significant cardiotoxic and developmental liabilities. This study provides crucial mechanistic insight into both its therapeutic and toxicological actions, establishing a translational foundation for its further development.

P4, N=100, Recruiting, Peking University Third Hospital

In this study, we evaluated the ability of elacridar, a dual P-gp and BCRP inhibitor, to overcome MDR in W1, an ovarian cancer cell line sensitive to Paclitaxel (PAC) and its PAC-resistant variants. These findings highlight elacridar as a promising compound for reversing MDR in ovarian cancer and emphasize the importance of 3D models in preclinical drug evaluation. Further studies in advanced in vitro and in vivo models are required to assess the potential of elacridar better.

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

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.

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.

P3, N=132, Terminated, Mannkind Corporation | N=234 --> 132 | Trial completion date: Dec 2028 --> Nov 2025 | Recruiting --> Terminated | Trial primary completion date: Aug 2026 --> Nov 2025; Futility