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DRUG:

Loramyc (miconazole muco-adhesive buccal tablet)

i
Other names: SO-1105
Associations
Trials
Company:
Fuji Pharma, GALT Pharma, Nxera Pharma, Valerio Therap
Drug class:
Cell membrane modulator
Associations
Trials
over3years
Miconazole induces autophagic death in glioblastoma cells via reactive oxygen species-mediated endoplasmic reticulum stress. (PubMed, Oncol Lett)
The inhibition of ER stress via treatment with 4-phenylbutyric acid or BiP knockdown reduced miconazole-induced autophagy and cell death. These findings suggest that miconazole induces autophagic cell death by inducing an ROS-dependent ER stress response in U251MG glioma cancer cells and provide new insights into the potential antiproliferative effects of miconazole.
Journal
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ERN1 (Endoplasmic Reticulum To Nucleus Signaling 1)
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Loramyc (miconazole muco-adhesive buccal tablet)
4years
Miconazole induces protective autophagy in bladder cancer cells. (PubMed, Environ Toxicol)
Finally, miconazole and autophagy inhibitor 3-methyladenine cotreatment further reduced the cell viability and induced apoptosis in BC cells, proving that miconazole provokes protective autophagy in BC cells. Our findings approve that miconazole has an antitumor effect in promoting cell apoptosis; however, its function of protective autophagy is needed to be concerned in cancer treatment.
Journal
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SQSTM1 (Sequestosome 1)
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Loramyc (miconazole muco-adhesive buccal tablet)
over4years
Miconazole inhibits signal transducer and activator of transcription 3 signaling by preventing its interaction with DNA damage-induced apoptosis suppressor. (PubMed, Cancer Sci)
Tyrosine phosphorylation of STAT3 at Y705 and expression of its targets, such as cyclin D1, survivin and snail, were decreased in miconazole-treated tumor tissues, as compared with those in vehicle-treated tumor tissues. These data suggest that miconazole exerts an anti-cancer effect by suppressing STAT3 activation through inhibiting DDIAS/STAT3 binding.
Journal
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CCND1 (Cyclin D1) • STAT3 (Signal Transducer And Activator Of Transcription 3) • BIRC5 (Baculoviral IAP repeat containing 5)
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CCND1 expression
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Loramyc (miconazole muco-adhesive buccal tablet)
over4years
Automated in vivo screen in zebrafish identifies clotrimazole as targeting a metabolic vulnerability in a melanoma model. (PubMed, Dev Biol)
We further tested two compounds for each of the 5 classes, and a farnesyltransferase inhibitor (Lonafarnib), that inhibits an essential post-translational modification of HRAS and suppresses the hyperpigmentation phenotype...Similar effects were observed with another hit of the same class, Miconazole. Furthermore, we show that the effects of clotrimazole are mediated by the inhibition of hexokinase activity, which is lethal to the abnormal metabolic profile of melanoma cells in vitro and in vivo. Thus, our study shows that the zebrafish can provide a phenotype-rich assay for fully automated screening approaches to identify drugs for synthetic lethal treatment in melanoma and suggest further testing of clotrimazole in combinatorial treatments.
Journal
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HRAS (Harvey rat sarcoma viral oncogene homolog) • HK1 (Hexokinase 1)
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Loramyc (miconazole muco-adhesive buccal tablet)
over4years
Miconazole Contributes to NRF2 Activation by Noncanonical P62-KEAP1 Pathway in Bladder Cancer Cells. (PubMed, Drug Des Devel Ther)
Pretreatment of bladder cancer cells with ROS scavengers abolished NRF2 expression and nuclear translocation, indicating that miconazole activates the noncanonical p62-KEAP1-NRF2 pathway, which is regulated by ROS production. Our study elucidates the mechanisms through which miconazole stimulates NRF2 which may contribute to cancer chemopreventive effects.
Journal
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KEAP1 (Kelch Like ECH Associated Protein 1)
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Loramyc (miconazole muco-adhesive buccal tablet)
over4years
Miconazole triggers various forms of cell death in human breast cancer MDA-MB-231 cells. (PubMed, Pharmazie)
The initial mechanism of MCZ-mediated cell death in human breast cancer MDA-MB-231 cells involves an increase in the Bax/Bcl-2 ratio, downregulation of apoptosis induced by Akt and p-Akt-473, a simultaneous upregulation of the receptor-interacting protein 3 (RIP3) and mixed lineage kinase domain-like (MLKL) protein expression, and ROS production to induce necroptosis. Our results suggest that MCZ may be a potential lead compound for the development of anti-breast cancer drugs.
Journal
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BCL2 (B-cell CLL/lymphoma 2) • BAX (BCL2-associated X protein)
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Loramyc (miconazole muco-adhesive buccal tablet)
almost5years
Inhibition of Drug Resistance of Staphylococcus aureus by Efflux Pump Inhibitor and Autolysis Inducer to Strengthen the Antibacterial Activity of β-lactam Drugs. (PubMed, Pol J Microbiol)
This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.
Journal
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IL6 (Interleukin 6)
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Loramyc (miconazole muco-adhesive buccal tablet)