P=N/A, N=248, Not yet recruiting, Tongji Medical College, Huazhong University of Science and Technology; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Tec

P2/3, N=129, Active, not recruiting, Gilead Sciences | Trial completion date: Dec 2024 --> Jun 2025

P2, N=50, Recruiting, Post Graduate Institute of Medical Education and Research, Chandigarh | N=30 --> 50 | Trial completion date: Jun 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P4, N=350, Recruiting, Gilead Sciences | Not yet recruiting --> Recruiting

P3, N=447, Completed, NEAT ID Foundation | Active, not recruiting --> Completed

The cytometric analysis showed that the tested compounds (especially EDAG-8) are inhibitors of BCRP, MDR1, and MRP1 efflux pumps (more potent than the reference compounds-novobiocin, verapamil, and MK-571). An in silico study correlates with these results, suggesting that the compound with the lowest binding energy to these transporters (EDAG-8) has a more favorable spatial structure affecting its anticancer activity, making it a promising candidate in the development of a novel anticancer agent for future breast cancer therapy.

P=N/A, N=15, Not yet recruiting, Peking University People's Hospital

We have reported that exo-C3-N-Dbn--Trp2 (13) as a lead ABCB1 inhibitor that is more effective than Verapamil...We correlate that the predictions based on the inhibitor interactions at the access tunnel provide clues about the design of improved ABCB1 inhibitors. This work lays the foundation for the design of a new class of inhibitors from a cyclo-L-Trp-L-Trp DKP scaffold.

P2, N=30, Not yet recruiting, Nantes University Hospital

P=N/A, N=165, Completed, University of Lausanne Hospitals | Active, not recruiting --> Completed

P1, N=36, Completed, Zenith Technology Corp Ltd | Not yet recruiting --> Completed

P=N/A, N=55, Recruiting, Universitaire Ziekenhuizen KU Leuven | Unknown status --> Recruiting | Trial primary completion date: Mar 2015 --> Mar 2025

By molecular simulations of ABCB1-substrate interactions, we generated a benzylated Cyclo-tryptophan (C3N-Dbn-Trp2) that inhibits ABCB1 activity with efficacy comparable to or better than the classical inhibitor, verapamil. C3N-Dbn-Trp2 restored chemotherapy sensitivity in drug-resistant human cancer cells with no adverse effect on cell proliferation. Our unique approach presents a promising lead toward developing effective ABCB1 inhibitors to treat drug-resistant cancers.

P=N/A, N=30, Enrolling by invitation, Beijing Tsinghua Chang Gung Hospital

P1, N=6, Terminated, German Cancer Research Center | N=18 --> 6 | Trial completion date: Feb 2025 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2024 --> Mar 2024; lack of efficacy paired with high toxicity

P=N/A, N=162, Active, not recruiting, State University of New York at Buffalo | Trial completion date: Jul 2023 --> Dec 2024 | Trial primary completion date: Jul 2023 --> Dec 2024

P=N/A, N=165, Active, not recruiting, University of Lausanne Hospitals | Recruiting --> Active, not recruiting

P1, N=10, Recruiting, Milton S. Hershey Medical Center | Trial completion date: May 2024 --> Jan 2025 | Trial primary completion date: May 2024 --> Dec 2024

P3, N=66, Terminated, Erasmus Medical Center | N=650 --> 66 | Trial completion date: Dec 2026 --> May 2024 | Recruiting --> Terminated | Trial primary completion date: Aug 2026 --> May 2024; futility

P=N/A, N=36, Completed, University of Edinburgh | Unknown status --> Completed

P=N/A, N=300, Completed, Baylor Research Institute | Unknown status --> Completed

P=N/A, N=30, Completed, University of Edinburgh | Unknown status --> Completed

P=N/A, N=104, Completed, Tomsk National Research Medical Center of the Russian Academy of Sciences | Active, not recruiting --> Completed

P4, N=75, Completed, The Crofoot Research Center, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Sep 2023 --> Apr 2024

P2, N=20, Completed, Seoul National University Hospital | Unknown status --> Completed | N=40 --> 20 | Trial completion date: Jun 2020 --> Jul 2023 | Trial primary completion date: Jun 2019 --> Jul 2023

Additionally, in microsomes where N-acetylcysteine was used as a trapping agent, N-acetylcysteine conjugates (M3, M4, M5 and M6) of four isomeric O-quinone-derived reactive metabolites were found...The IC50 shift assay showed time-dependent inhibition of CYP3A4, 2C9, 2E1, 2C8 and 2D6 by PLG. This research contributes to the understanding of PLG-induced enzyme inhibition and bioactivation.

P4, N=60, Recruiting, Maastricht University Medical Center | Not yet recruiting --> Recruiting

P4, N=350, Not yet recruiting, Gilead Sciences

P=N/A, N=249, Completed, Medical University of Graz | Recruiting --> Completed | Trial completion date: Dec 2022 --> Aug 2023 | Trial primary completion date: Sep 2022 --> Aug 2023

P1, N=30, Not yet recruiting, University Health Network, Toronto | Trial completion date: Aug 2022 --> Jun 2027 | Trial primary completion date: Aug 2022 --> Jun 2025

Moreover, the DEX-treated group exhibited an increase in Rho123 efflux, and it was reversed by treatment with the P-gp inhibitor verapamil or Ezr siRNA. The decrease in cell viability with paclitaxel (PTX) treatment was mitigated by pretreatment with DEX. The increased expression and activation of P-gp during the progression of lung cancer MET was regulated by Ezr. The regulatory mechanism of P-gp expression and activity may differ depending on the cell status.

This study provided evidence of the potential of Amaryllidaceae alkaloids as lead candidates for the development of MDR reversal agents.

In this study, structural modification of a third-generation P-gp inhibitor WK-X-34 based on bioisosteric and fragment-growing strategies led to the discovery of the adamantane derivative PID-9, which exhibited the best MDR reversal activity (IC50 = 0.1338 μM, RF = 78.6) in this series, exceeding those of the reported P-gp inhibitors verapamil and WK-X-34...Furthermore, the mechanism studies revealed that the reversal activity of adamantane derivatives PID-5, PID-7, and PID-9 stemmed from the inhibition of P-gp efflux. These results indicated that compound PID-9 is the most effective P-gp inhibitor among them with low toxicity and high MDR reversal activity, which provided a fundamental structural reference for further discovery of novel, effective, and non-toxic P-gp inhibitors.

P3, N=36, Completed, Chelsea and Westminster NHS Foundation Trust | Active, not recruiting --> Completed

P2, N=170, Active, not recruiting, Cambridge University Hospitals NHS Foundation Trust | Recruiting --> Active, not recruiting

P2, N=31, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> Dec 2023 | Trial primary completion date: Apr 2024 --> Dec 2023

Upregulation of ABCB1 through locus amplification represents a novel, conserved mechanism of PDAC paclitaxel resistance. Kinase inhibitors identified in this study can be further (pre) clinically explored as therapeutic strategies to overcome paclitaxel resistance in PDAC.

P4, N=30, Recruiting, East Carolina University

P=N/A, N=77, Active, not recruiting, Jaeb Center for Health Research

P=N/A, N=130, Recruiting, Radboud University Medical Center

P2/3, N=130, Recruiting, Gilead Sciences

Our results suggest that verapamil inhibits tumor growth by modulating NFAT2 expression and enhancing tumor immune responses to PD1ab, which can be harnessed for cervical cancer therapy, especially for patients with comorbid hypertension. Indeed, further clinical trials are warranted to increase the robustness of our findings.