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.

P2, N=30, Recruiting, Radboud University Medical Center | Trial completion date: Jun 2023 --> Jul 2025

P=N/A, N=165, Recruiting, University of Lausanne Hospitals | Trial completion date: Dec 2023 --> May 2024 | Trial primary completion date: Dec 2023 --> Mar 2024

P2, N=22, Completed, R. Kiplin Guy | Phase classification: P2a --> P2

According to EORTC criteria, two patients (10%) had a probable IFI on day 14, and antifungal therapy with liposomal amphotericin B was started [3]...Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia... Twenty patients were included: 9 were women (45%) with a median age of 67 years old (±10. 5) and a median Charlson Comorbidity Index of 5 (±1. 3).

P4, N=210, Enrolling by invitation, Insel Gruppe AG, University Hospital Bern | Recruiting --> Enrolling by invitation | Trial completion date: Aug 2027 --> Dec 2027 | Trial primary completion date: Aug 2025 --> Nov 2025

Our findings underscore the potential of mosloflavone as a novel dual modulator of STAT3 and P-gp, indicating it is a promising candidate for overcoming MDR in cancer treatment.

Although both the mutants were expressed at normal levels at the cell surface, the 6Y mutant failed to transport all the tested substrates except Bodipy-verapamil, whereas the 9Y mutant effluxed all tested substrates in a manner very similar to that of the wild-type protein...This is the first evidence for the existence of second-site suppressors in human P-gp that allow recovery of the loss of transport function caused by primary mutations. Further study of such mutations could facilitate mapping of the communication pathway between the substrate-binding pocket and the NBDs of P-gp and possibly other ABC drug transporters.

We observed three cases of invasive fungal infections (8.5%), once again with no differences between the two groups. Our study suggest that the concomitant administration of PCZ and midostaurin results effective and safe for FLT3-mut AML patients.

In addition, many CADs that may potentially undergo lysosomal trapping, which include imipramine, propranolol, verapamil, and some others, were found to inhibit SLC49A4-AA-mediated pyrilamine transport, suggesting their affinity for SLC49A4. Significance Statement SLC49A4 mediates the transport of pyrilamine in a H-coupled manner at the lysosomal membrane. This could be a newly identified mechanism for lysosomal export involved in its lysosomal trapping.

Overcoming resistance to paclitaxel by CYP3A5 inhibition may lead to an increased efficacy of the gemcitabine and nab-paclitaxel regimen. Safety, efficacy, PK, and RDE data need to be acquired before investigating this combination in a large-scale clinical study.

P4, N=24, Recruiting, Cedars-Sinai Medical Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2024

P2, N=30, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

P4, N=210, Recruiting, Insel Gruppe AG, University Hospital Bern | Not yet recruiting --> Recruiting

The most frequently reported treatment-related AEs were erythema (n=14; 88%) and headache (n=11; 69%) in Part 1 and headache (n=7; 44%) in Part 2. The results of this study indicate that coadministration of encorafenib with strong or moderate CYP3A4 inhibitors should be avoided.

A previous study has shown that ARN14988 is more cytotoxic to GBM cells compared to US Food and Drug Administration-approved temozolomide...The monitored transitions were m/z 391.20 → m/z 147.00 for ARN14988, and m/z 455.30 → m/z 165.00 for verapamil (internal standard) in positive electrospray ionization...The selectivity, sensitivity, matrix effect, recovery, stability, inter-day and intraday accuracy and precision were determined using four quality control samples. This validated method was successfully applied to the pharmacokinetic study of ARN14988 in mice.

These results demonstrate that menthol causes hepatocellular carcinoma to acquire resistance to anticancer drugs such as EPI and CIS by MRP2 induction.

Amphotericin B, posaconazole, and voriconazole were successively used for antifungal therapy. Early diagnosis and treatment should be carried out. Combined antifungal therapy is recommended, and surgery is helpful to improve the patient's condition.