The elevated expression level of GPX4 in oral cancer biopsies was also found to correlate with a poor prognosis. Together, these results provide evidence that TFP selectively induces GPX4-mediated, autophagy-dependent ferroptosis, thereby exerting anti-cancer effects against oral cancer and preventable death.

P=N/A, N=40, Active, not recruiting, Seattle Institute for Biomedical and Clinical Research | N=20 --> 40

P2, N=705, Recruiting, Intra-Cellular Therapies, Inc. | Trial completion date: Jan 2027 --> Jun 2027 | Trial primary completion date: Dec 2026 --> Jun 2027

P2, N=570, Recruiting, Intra-Cellular Therapies, Inc.

P=N/A, N=6, Completed, McMaster University | Unknown status --> Completed | N=20 --> 6

P=N/A, N=200, Recruiting, Centre Hospitalier St Anne | Not yet recruiting --> Recruiting

The calmodulin-inhibitors trifluoperazine and ophiobolin A mediated delayed activation of ADAM10, which apparently did not depend on intracellular Ca2+ in the case of trifluoperazine...Finally, ADAM10 activation was observed after the entry of Ca2+ through certain channels, such as canonical members of transient receptor potential (TRP) channels. Therefore, the opening of particular channels for Ca2+ entry points and subsequent Ca2+ flux as well as the temporal aspects of the consequent increase in Ca2+ levels, must be considered for future therapeutic options involving the increasing or decreasing ADAM10 activity.

P1, N=95, Active, not recruiting, Teva Branded Pharmaceutical Products R&D, Inc. | Recruiting --> Active, not recruiting

ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies.

P2, N=320, Recruiting, Intra-Cellular Therapies, Inc.

Our results indicate that serum IL-2, IL-8, IL-10, and TNF-α levels may be involved in the pathophysiological mechanisms of schizophrenia and correlate with the effects of olanzapine.

P3, N=654, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

The synergistic combination of PER and TMZ has potential as a novel combination treatment strategy for GBM.

P3, N=164, Completed, Cairo University | Recruiting --> Completed

Our findings from this computational study presents cyanidin (-8.822 kcal/mol) as better binder to the allosteric site of MALT1 based on the molecular docking and pharmacokinetic profiling than thioridazine...Hence, cyanidin is a potential allosteric inhibitor of MALT1. However, an urgent need for in vitro and in vivo validations is required to ascertain the efficacy of cyanidin in the fight against cancer and other MALT1-related diseases.

P=N/A, N=200, Not yet recruiting, Centre Hospitalier St Anne

P4, N=60, Completed, All India Institute of Medical Sciences, Bhubaneswar | Recruiting --> Completed

P2, N=170, Enrolling by invitation, Englewood Hospital and Medical Center | Trial completion date: Dec 2023 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026

We investigated fluspirilene, perphenazine, and sulpiride, three classic anti-schizophrenic drugs, as possible anti-GBM agents. In fluspirilene-treated cells, FOXM1 protein was decreased, indicating that KIF20A was downregulated in the presence of the drug due to decreased FOXM1 protein. These results demonstrate that fluspirilene is an effective anti-GBM agent that works by suppressing the FOXM1-KIF20A oncogenic axis.

P2, N=36, Not yet recruiting, Austin Hospital

In vivo, TFP inhibited subcutaneous OS cell proliferation and induced OS cell apoptosis without noticeable side effects. In conclusion, our findings imply that TFP is a potential treatment for OS.

P=N/A, N=200, Completed, Central South University | Recruiting --> Completed

P2, N=156, Not yet recruiting, Second Affiliated Hospital of Nanchang University

These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

P1, N=50, Not yet recruiting, Lawson Health Research Institute

The research emphasizes the significance of SUSD3 as a potential marker for BC, providing insights into the underlying molecular mechanisms implicated in tumorigenesis. SUSD3 holds promise in helping the classification of breast cancer pathological groups, predicting prognosis, and facilitating targeted therapy.

P2, N=370, Recruiting, Intra-Cellular Therapies, Inc.

P=N/A, N=48, Recruiting, Rajavithi Hospital | Not yet recruiting --> Recruiting

However, cotreatment with Cevimeline significantly reversed the lipid metabolic disturbance and adipose tissue accumulation, as well as the upregulation of the hepatic Alk signaling caused by Olanzapine. This study demonstrates evidence that Olanzapine may cause metabolic disturbance by modulating hepatic Alk signaling via M3R, which provides novel insight for modulating the hepatic Alk signaling and potential interventions for targeting metabolic disorders.

We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ suppresses mPFC-NE-CLOCK axis to reverse chronic stress-induced anxiety-like behaviors and lung cancer stemness. Decreased NE-releasing prevents activation of ADRB2-cAMP-PKA-CREB pathway to inhibit CLOCK transcription, thus reversing lung cancer stem-like traits and chemoresistance under chronic stress.

P1/2, N=30, Active, not recruiting, University of Pennsylvania | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P3, N=138, Recruiting, Mahidol University

Cytotoxicities of 28 PTZ derivatives (1-28) screened against Hep3B and SkHep1 liver cancer cell lines revealed five intermediate and five novel leads along with trifluoperazine (TFP), prochlorperazine (PCP), and perphenazine, which are relatively more cytotoxic than the basic PTZ core. Moreover, they modulated the cholinesterase activity or expression of ACHE in a cancer cell line-specific manner, and compound 10 significantly inhibited the cholinesterase activity in zebrafish. Accordingly, using a successful combination of in silico, in vitro, and in vivo approaches, we identified several lead anticancer and cholinesterase modulatory PTZ derivatives for future research.

Our drug repurposing analysis and molecular docking simulations suggested eight drug candidates for LUAD such as heat shock protein 90 inhibitors, cardiac glycosides, an antipsychotic agent (trifluoperazine), and a calcium ionophore (ionomycin). In summary, this study identifies several promising leads on systems biomarkers and drug candidates for LUAD. The findings also attest to the importance of integrative bioinformatics, structural biology and machine learning techniques in biomarker discovery, and precision oncology research and development.

P2, N=705, Recruiting, Intra-Cellular Therapies, Inc.

TLK1 phosphorylation is an important event in DUV irradiation. DUV irradiation combined with TLK1 inhibition has therapeutic potential in pancreatic cancer cells.

P3, N=62, Terminated, University of Michigan Rogel Cancer Center | Active, not recruiting --> Terminated; Lack of Patient Population

P3, N=360, Recruiting, Alliance for Clinical Trials in Oncology | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Apr 2024 --> May 2026

P4, N=30, Not yet recruiting, University of Southern California | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jul 2024 --> Jul 2026

P3, N=0, Withdrawn, Mayo Clinic | Trial completion date: Jun 2024 --> Dec 2024

P1, N=12, Recruiting, Intra-Cellular Therapies, Inc. | Not yet recruiting --> Recruiting

P2, N=66, Recruiting, OHSU Knight Cancer Institute | Suspended --> Recruiting | N=44 --> 66 | Trial completion date: Nov 2024 --> Dec 2025 | Trial primary completion date: Nov 2024 --> Jun 2025