Repositioning of Cefuroxime as novel selective inhibitor of the thyroid hormone activating enzyme type 2 deiodinase Article Swipe
Serena Sagliocchi
,
Melania Murolo
,
Annunziata Gaetana Cicatiello
,
Caterina Miro
,
Annarita Nappi
,
Emery Di Cicco
,
Sepehr Torabinejad
,
Evelina La Civita
,
Veronica Romano
,
Daniela Terracciano
,
Mariano Stornaiuolo
,
Monica Dentice
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.phrs.2023.106685
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1016/j.phrs.2023.106685
The iodothyronine deiodinases constitute a family of three selenoenzymes regulating the intracellular metabolism of Thyroid Hormones (THs, T4 and T3) and impacting on several physiological processes, including energy metabolism, development and cell differentiation. The type 1, 2 and 3 deiodinases (D1, D2, and D3), are sensitive, rate-limiting components within the TH axis, and rapidly control TH action in physiological conditions or disease. Notably, several human pathologies are characterized by deiodinases deregulation (e.g., inflammation, osteoporosis, metabolic syndrome, muscle wasting and cancer). Consequently, these enzymes are golden targets for the identification and development of pharmacological compounds endowed with modulatory activities. However, until now, the portfolio of inhibitors for deiodinases is limited and the few active compounds lack selectivity. Here, we describe the cephalosporin Cefuroxime as a novel D2 specific inhibitor. In both in vivo and in vitro settings, Cefuroxime acts as a selective inhibitor of D2 activity, without altering the enzymatic activity of D1 and D3. By inhibiting TH activation in target tissues, Cefuroxime alters the sensitivity of the hypothalamus-pituitary axis and interferes with the central regulation of THs levels, and is thus eligible as a potential new regulator of hyperthyroid pathologies, which affect thousands of patients worldwide.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.phrs.2023.106685
- OA Status
- gold
- Cited By
- 11
- References
- 44
- Related Works
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- OpenAlex ID
- https://openalex.org/W4319967921
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4319967921Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.phrs.2023.106685Digital Object Identifier
- Title
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Repositioning of Cefuroxime as novel selective inhibitor of the thyroid hormone activating enzyme type 2 deiodinaseWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
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2023-02-10Full publication date if available
- Authors
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Serena Sagliocchi, Melania Murolo, Annunziata Gaetana Cicatiello, Caterina Miro, Annarita Nappi, Emery Di Cicco, Sepehr Torabinejad, Evelina La Civita, Veronica Romano, Daniela Terracciano, Mariano Stornaiuolo, Monica DenticeList of authors in order
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https://doi.org/10.1016/j.phrs.2023.106685Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1016/j.phrs.2023.106685Direct OA link when available
- Concepts
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Deiodinase, Chemistry, Hormone, Pharmacology, Internal medicine, Endocrinology, Biology, Biochemistry, Medicine, Thyroid hormonesTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
11Total citation count in OpenAlex
- Citations by year (recent)
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2025: 7, 2024: 1, 2023: 3Per-year citation counts (last 5 years)
- References (count)
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44Number of works referenced by this work
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-
10Other works algorithmically related by OpenAlex
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