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Ketoconazole - Europe PMC

Summarized by Plex Scholar
Last Updated: 11 September 2022

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An FDA-Approved Antifungal, Ketoconazole, and Its Novel Derivative Suppress tGLI1-Mediated Breast Cancer Brain Metastasis by Inhibiting the DNA-Binding Activity of Brain Metastasis-Promoting Transcription Factor tGLI1.

truncated glioma-associated oncogene homolog 1, truncated glioma-associated oncogene homolog 1, The aim of this research is to find pharmacological inhibitors targeted at a newly discovered novel mediator of breast cancer brain metastasis. We tested 1527 compounds on two sets of isogenic breast cancer and brain-tropic breast cancer cell lines engineered to stably identify the target, the tGLI1 gene, but not tGLI1-negative breast cancer cells and breast cancer stem cells, but not tGLI1-positive breast cancer cells and breast cancer stem cells. Two experimental mouse metastasis studies have shown that systemic KCZ administration delayed the preferential brain metastasis of tGLI1-positive breast cancer and slowed the progression of adult tGLI1-positive breast cancer without liver toxicities in established tGLI1-positive BCBM without liver toxicities. Our research establishes the logic behind using KCZ and KCZ-7 for treating and preventing BCBM, as well as their mechanism of action.

Source link: https://europepmc.org/article/MED/36077791


Functionalized PEG-PLA nanoparticles for brain targeted delivery of ketoconazole contribute to pregnane X receptor overexpressing in drug-resistant epilepsy.

Objection: To overcome pregnane X receptor's overactivity for the treatment of drug-resistant epilepsy, the development of a novelized PEG-PLA nanoparticle system containing ketoconazole is aimed. KCZ was created as a therapeutic approach for DRE restricted by its lethal hepatotoxicity and minute brain concentration. With carbamazepine treatment, an epilepsy model of epilepsy in a kainic acid-induced mouse model of epilepsy was tested. In mice treated with NPs/KCZ+CBZ, the CBZ content of brain tissues was significantly higher than those treated with CBZ alone. In the NPs/KCZ+CBZ group, a significantly reduced expression level of PXR and its downstream proteins was discovered, as compared to those in the control and CBZ groups. Conclusion Our findings showed that NPs/KCZ met the epileptic foci-targeted delivery of KCZ and improved the CBZ's DRE's effectiveness by attenuating PXR's overactivity.

Source link: https://europepmc.org/article/MED/36037622

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions