P3, N=174, Recruiting, Intra-Cellular Therapies, Inc.

P=N/A, N=300, Completed, University of Maryland, Baltimore | Active, not recruiting --> Completed | Trial completion date: Dec 2024 --> Sep 2024

P4, N=350, Recruiting, Vanderbilt University Medical Center | Trial primary completion date: Jul 2024 --> Jul 2025

P=N/A, N=36, Completed, University of Auckland, Department of Psychological Medicine | Not yet recruiting --> Completed

P3, N=228, Completed, Intra-Cellular Therapies, Inc. | Active, not recruiting --> Completed

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

Based on a clinical staged small molecular hClpP activator ONC201, a class of novel hClpP agonists with a [1,8]naphthyridinone scaffold were designed, synthesized and evaluated in a series of biochemical and biological assays. Mechanism studies for the representative compound F20 indicated that it can potently bind to and activate hClpP, efficiently promote the degradation of hClpP substrates, robustly induce ATF4/CHOP regulated integrated stress responses, strongly inhibit cell growth and effectively induce apoptosis in a subset of cancer cell lines. F20 showed good PK profiles when dosed by intravenous injection and exhibited moderate oral bioavailability in mice.

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.

Importantly, B2R-D2R complexes were detected in human prolactinomas and nonfunctioning pituitary adenomas (NFPA), but not in mixed (prolactin + growth hormone) secreting adenomas. These results suggest that overexpression of B2R in resistant prolactinomas may promote the formation of B2R-D2R complexes, with B2R precluding D2R signaling, thus generating resistance to D2R agonists.

P3, N=470, Recruiting, Intra-Cellular Therapies, Inc. | Trial completion date: Oct 2025 --> Oct 2026 | Trial primary completion date: Oct 2025 --> Sep 2026

P1, N=32, Recruiting, Capital Medical University | Not yet recruiting --> Recruiting

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

We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.

P1, N=32, Not yet recruiting, Capital Medical University

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.

The data suggest a possible therapeutic route for schizophrenia patients.

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.

Previous studies have shown that chlorpromazine (CPZ) can inhibit YAP1 expression...Collectively, our findings indicate that FOXP3 competitively binds TEAD4 to regulate YAP1 localization in the nucleus and cytoplasm to suppress NPC progression. Consequently, FOXP3 may be a prognostic indicator for HNSCC.

Imipridones are a promising strategy for further testing and development in mUM.

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

P1, N=8, Withdrawn, Lyndra Australia Pty Ltd | Not yet recruiting --> Withdrawn

P1, N=20, Active, not recruiting, University of Nebraska | Trial primary completion date: Aug 2024 --> Oct 2026

P4, N=24, Recruiting, Centre Hospitalier Universitaire, Amiens

P=N/A, N=300, Active, not recruiting, University of Maryland, Baltimore | Trial primary completion date: Jun 2024 --> Jan 2024

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

P3, N=157, Completed, Advocate Health Care | N=288 --> 157

Cabergoline has a stronger affinity for the D2R receptor and longer half-life than L-Dopa, leading to lactotroph apoptosis, tumor shrinkage, and rapid and maintained normalization of PRL levels, with a better side-effect profile. Patients with DHPR deficiency need to be actively monitored for symptomatic hyperprolactinemia, as L-Dopa monotherapy is insufficient to suppress PRL secretion, leading to lactotroph hypertrophy and proliferation over time and development of prolactinomas in later life.

Emerging evidences indicate DRD2 is involved in the CRC biology, and the association between DRD2 and CRC could be utilized in treating CRC. This study selected DRD2 antagonists with anticancer activity to elucidate the possibility of DRD2 antagonists as new therapeutics for treating CRC.

We conclude that a therapeutic window for dopamine receptor antagonists in combination with radiation potentially exists, making it a novel combination therapy against glioblastoma. Normal tissue toxicity following this treatment scheme likely differs depending on age and sex and should be taken into consideration when designing clinical trials.

P3, N=100, Recruiting, Benaroya Research Institute | Not yet recruiting --> Recruiting

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

P2, N=120, Completed, Neurogastrx, Inc. | Active, not recruiting --> Completed

P=N/A, N=20, Completed, Centre Hospitalier Universitaire de Saint Etienne

Notably, ±RHPC8-CSP was significantly taken up by SR-expressing TAMs thus resulting in macrophage polarization from M2 to M1, as exhibited by markedly reduced expression of immunosuppressive cytokines released by TAMs, including TGF-β, IL-10, and VEGF. In conclusion, the designed ±RHPC8-CSP nanoconjugate presented an effective nanodrug delivery system for brain cancer treatment.

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

P2, N=350, Active, not recruiting, LB Pharmaceuticals Inc. | Recruiting --> Active, not recruiting

P1, N=6, Not yet recruiting, Beijing Tiantan Hospital

P=N/A, N=338, Suspended, The Affiliated Hospital of Shandong Second Medical University; The Affiliated Hospital of Shandong Second Medical University | Not yet recruiting --> Suspended

P=N/A, N=300, Not yet recruiting, The Fifth Affiliated Hospital of Xinjiang Medical University; The Fifth Affiliated Hospital of Xinjiang Medical University