Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity
BMP‐1/tolloid‐like proteinases belong to the astacin family of human metalloproteinases, together with meprins and ovastacin. They represent promising targets to treat or prevent a wide range of diseases such as fibrotic disorders or cancer. However, the study of their pathophysiological roles is st...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2018-12-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12540 |
| _version_ | 1827990598796181504 |
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| author | Maya Talantikite Pascaline Lécorché Fabrice Beau Odile Damour Christoph Becker‐Pauly Wen‐Bin Ho Vincent Dive Sandrine Vadon‐Le Goff Catherine Moali |
| author_facet | Maya Talantikite Pascaline Lécorché Fabrice Beau Odile Damour Christoph Becker‐Pauly Wen‐Bin Ho Vincent Dive Sandrine Vadon‐Le Goff Catherine Moali |
| author_sort | Maya Talantikite |
| collection | DOAJ |
| description | BMP‐1/tolloid‐like proteinases belong to the astacin family of human metalloproteinases, together with meprins and ovastacin. They represent promising targets to treat or prevent a wide range of diseases such as fibrotic disorders or cancer. However, the study of their pathophysiological roles is still impaired by the lack of well‐characterized inhibitors and the questions that remain regarding their selectivity and in vivo efficiency. As a first step towards the identification of suitable tools to be used in functional studies, we have undertaken a systematic comparison of seven molecules known to affect the proteolytic activity of human astacins including three hydroxamates (FG‐2575, UK383,367, S33A), the protein sizzled, a new phosphinic inhibitor (RXP‐1001) and broad‐spectrum protease inhibitors (GM6001, actinonin). Their efficacy in vitro, their cellular toxicity and efficacy in cell cultures were thoroughly characterized. We found that these molecules display very different potency and selectivity profiles, with hydroxamate FG‐2575 and the protein sizzled being very powerful and selective inhibitors of BMP‐1, whereas phosphinic peptide RXP‐1001 behaves as a broad‐spectrum inhibitor of astacins. Their use should therefore be carefully considered in agreement with the aim of the study to avoid result misinterpretation. |
| first_indexed | 2024-04-10T00:37:59Z |
| format | Article |
| id | doaj.art-eb3e5e39b95545e6ab8e6960ceae5cd1 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-10T00:37:59Z |
| publishDate | 2018-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-eb3e5e39b95545e6ab8e6960ceae5cd12023-03-14T13:06:01ZengWileyFEBS Open Bio2211-54632018-12-018122011202110.1002/2211-5463.12540Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicityMaya Talantikite0Pascaline Lécorché1Fabrice Beau2Odile Damour3Christoph Becker‐Pauly4Wen‐Bin Ho5Vincent Dive6Sandrine Vadon‐Le Goff7Catherine Moali8Tissue Biology and Therapeutic Engineering Unit (LBTI) UMR5305, CNRS Univ Lyon Université Claude Bernard Lyon1 FranceCEA Saclay Institut Frédéric Joliot Direction de la recherche fondamentale SIMOPRO Gif‐sur‐Yvette FranceCEA Saclay Institut Frédéric Joliot Direction de la recherche fondamentale SIMOPRO Gif‐sur‐Yvette FranceTissue Biology and Therapeutic Engineering Unit (LBTI) UMR5305, CNRS Univ Lyon Université Claude Bernard Lyon1 FranceInstitute of Biochemistry Unit for Degradomics of the Protease Web Christian‐Albrechts‐University Kiel GermanyFibroGen Inc San Francisco CA USACEA Saclay Institut Frédéric Joliot Direction de la recherche fondamentale SIMOPRO Gif‐sur‐Yvette FranceTissue Biology and Therapeutic Engineering Unit (LBTI) UMR5305, CNRS Univ Lyon Université Claude Bernard Lyon1 FranceTissue Biology and Therapeutic Engineering Unit (LBTI) UMR5305, CNRS Univ Lyon Université Claude Bernard Lyon1 FranceBMP‐1/tolloid‐like proteinases belong to the astacin family of human metalloproteinases, together with meprins and ovastacin. They represent promising targets to treat or prevent a wide range of diseases such as fibrotic disorders or cancer. However, the study of their pathophysiological roles is still impaired by the lack of well‐characterized inhibitors and the questions that remain regarding their selectivity and in vivo efficiency. As a first step towards the identification of suitable tools to be used in functional studies, we have undertaken a systematic comparison of seven molecules known to affect the proteolytic activity of human astacins including three hydroxamates (FG‐2575, UK383,367, S33A), the protein sizzled, a new phosphinic inhibitor (RXP‐1001) and broad‐spectrum protease inhibitors (GM6001, actinonin). Their efficacy in vitro, their cellular toxicity and efficacy in cell cultures were thoroughly characterized. We found that these molecules display very different potency and selectivity profiles, with hydroxamate FG‐2575 and the protein sizzled being very powerful and selective inhibitors of BMP‐1, whereas phosphinic peptide RXP‐1001 behaves as a broad‐spectrum inhibitor of astacins. Their use should therefore be carefully considered in agreement with the aim of the study to avoid result misinterpretation.https://doi.org/10.1002/2211-5463.12540astacincorneaextracellular matrixfibrotic disordersmetalloproteinaseprotease inhibition |
| spellingShingle | Maya Talantikite Pascaline Lécorché Fabrice Beau Odile Damour Christoph Becker‐Pauly Wen‐Bin Ho Vincent Dive Sandrine Vadon‐Le Goff Catherine Moali Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity FEBS Open Bio astacin cornea extracellular matrix fibrotic disorders metalloproteinase protease inhibition |
| title | Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity |
| title_full | Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity |
| title_fullStr | Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity |
| title_full_unstemmed | Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity |
| title_short | Inhibitors of BMP‐1/tolloid‐like proteinases: efficacy, selectivity and cellular toxicity |
| title_sort | inhibitors of bmp 1 tolloid like proteinases efficacy selectivity and cellular toxicity |
| topic | astacin cornea extracellular matrix fibrotic disorders metalloproteinase protease inhibition |
| url | https://doi.org/10.1002/2211-5463.12540 |
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