This further suggests that if chlorpromazine binding alters coupling between the PAS/CNBH domain ring, VSD and pore, as predicted by the network analysis, these alterations occur at potential more depolarized than the ones eliciting the Cole-Moore shift. Taken together, our study provides an insight into the allosteric pathways of EAG1 channel regulation by small molecule PAS domain binders.

We demonstrate that CPZ, alone or in combination with temozolomide (TMZ), the current standard of care, activates the cGAS-STING signaling pathway, thus promoting anti-tumor immune responses. This study uncovers that CPZ exerts a previously unrecognized anti-cancer immunomodulatory activity, remodeling the immune microenvironment and enhancing the anti-tumor immune response. By overcoming TMZ resistance, CPZ not only exerts a direct anti-neoplastic effect, but also sensitizes GBM cells to standard therapy.

P4, N=31, Completed, Vanderbilt University Medical Center | Recruiting --> Completed | N=350 --> 31

P=N/A, N=104, Not yet recruiting, Huashan Hospital Fudan University; Huashan Hospital Fudan University

P2, N=128, Not yet recruiting, University of Calgary | N=36 --> 128 | Trial completion date: Oct 2027 --> Jan 2028 | Trial primary completion date: Sep 2027 --> Dec 2027

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

P2/3, N=42, Recruiting, M.D. Anderson Cancer Center | N=30 --> 42

We could prove that a structure-based drug repurposing approach is an effective strategy to produce a promising antiangiogenic repurposed drug that could also inhibit VEGFR2 in breast cancer. Although risperidone showed modest potency, its clinical availability and repurposing potential support further evaluation in preclinical and clinical settings.

Although FLT3 tyrosine kinase inhibitors (TKIs), such as quizartinib (Quiz) and gilteritinib, have improved clinical outcomes, secondary TKD mutations, particularly the gatekeeper mutation F691L, confer significant resistance. Expression of constitutively active STAT5 partially rescued CPZ-induced growth inhibition. These findings suggest that STAT5 suppression is a key mechanism of CPZ's antileukemic activity and support its potential as a therapeutic strategy for FLT3-ITD-positive AML.

In this study, drug repurposing agent's metformin, chlorpromazine (CPZ) alone and combine were tested on both clinical and laboratory ovarian cancer samples to evaluate on hemocytometer and clonogenic assay for dead cell and proliferation respectively. The resulting data were analyzed to achieve successfully known target region and worked as a bridge between clinical and laboratory model. The insights gained from this study not only validate OVCAR3 as a representative model for HGSOC but also provide a foundation for developing targeted therapeutic strategies.

Notably, risperidone (SM-2) emerged as a potential inhibitory regulator capable of disrupting the cascade effects mediated by the GDF15-GFRAL axis, underscoring its therapeutic relevance. This study identifies the GDF15-GFRAL signaling axis as a critical regulator of oxidative stress and immune evasion in HNSCC and demonstrates that the novel small-molecule SM-2 effectively targets this pathway, highlighting its potential as a promising therapeutic strategy.

There was higher overall risk of SI in patients with chronic schizophrenia. SI might be associated with psychotic symptoms, depression, insomnia, medication side effects, and increased levels of inflammatory cytokines. In clinical practice, doctors should take prompt preventive measures in patients combining suicidal risk factors.