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Similar Publications

From Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.

J Comput Chem

January 2025

Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, New South Wales, Australia.

Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions.

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Fluspirilene exerts an anti-glioblastoma effect through suppression of the FOXM1-KIF20A axis.

Neoplasma

August 2024

Department of Anesthesiology, The Affiliated Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.

Article Synopsis
  • Fluspirilene, a classic anti-schizophrenic drug, shows significant potential as a treatment for human glioblastoma (GBM), outperforming perphenazine and sulpiride in anti-GBM effects.
  • Molecular studies show fluspirilene inhibits GBM cell proliferation and migration while increasing apoptosis, particularly affecting U87MG and U251 cell lines.
  • The drug's mechanism involves downregulating KIF20A through the oncogenic transcription factor FOXM1, indicating its role in the suppression of growth in GBM cells.
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Drug repurposing for Mpox: Discovery of small molecules as potential inhibitors against DNA-dependent RNA polymerase using molecular modeling approach.

J Cell Biochem

May 2023

Department of Microbiology and Immunology, Department of Paediatrics, IWK Health Center, Canadian Centre for Vaccinology (CCfV), Faculty of Medicine, Dalhousie University, Halifax, Canada.

Mpox (formerly Monkeypox), a zoonotic illness caused by the Mpox virus, belongs to the Orthopoxvirus genus in the family Poxviridae. To design and develop effective antiviral therapeutics against DNA viruses, the DNA-dependent RNA polymerase (DdRp) of poxviruses has emerged as a promising drug target. In the present study, we modeled the three-dimensional (3D) structure of DdRp using a template-based homology approach.

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Despite significant progress in understanding the pathogenesis of type 2 diabetes (T2D), the condition remains difficult to manage. Hence, new therapeutic options targeting unique mechanisms of action are required. We have previously observed that elevated skeletal muscle succinyl CoA:3-ketoacid CoA transferase (SCOT) activity, the rate-limiting enzyme of ketone oxidation, contributes to the hyperglycemia characterizing obesity and T2D.

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The persistent increase of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) infections negatively impacts Tuberculosis treatment outcomes. Host-directed therapies (HDT) pose an complementing strategy, particularly since Mtb is highly successful in evading host-defense by manipulating host-signaling pathways. Here, we screened a library containing autophagy-modulating compounds for their ability to inhibit intracellular Mtb-bacteria.

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