Discovery and Optimization of Selective Inhibitors of Meprin α (Part II)
Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/3/197 |
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| author | Chao Wang Juan Diez Hajeung Park Christoph Becker-Pauly Gregg B. Fields Timothy P. Spicer Louis D. Scampavia Dmitriy Minond Thomas D. Bannister |
| author_facet | Chao Wang Juan Diez Hajeung Park Christoph Becker-Pauly Gregg B. Fields Timothy P. Spicer Louis D. Scampavia Dmitriy Minond Thomas D. Bannister |
| author_sort | Chao Wang |
| collection | DOAJ |
| description | Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition. |
| first_indexed | 2024-03-09T06:16:04Z |
| format | Article |
| id | doaj.art-d8cceaa6cbc14f5f907dec89399d1671 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T06:16:04Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d8cceaa6cbc14f5f907dec89399d16712023-12-03T11:53:04ZengMDPI AGPharmaceuticals1424-82472021-02-0114319710.3390/ph14030197Discovery and Optimization of Selective Inhibitors of Meprin α (Part II)Chao Wang0Juan Diez1Hajeung Park2Christoph Becker-Pauly3Gregg B. Fields4Timothy P. Spicer5Louis D. Scampavia6Dmitriy Minond7Thomas D. Bannister8Department of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USARumbaugh-Goodwin Institute for Cancer Research, Nova Southeastern University, 3321 College Avenue, CCR r.605, Fort Lauderdale, FL 33314, USADepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USAThe Scripps Research Molecular Screening Center, Scripps Research, Jupiter, FL 33458, USAUnit for Degradomics of the Protease Web, Institute of Biochemistry, University of Kiel, Rudolf-Höber-Str.1, 24118 Kiel, GermanyDepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USADepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USADepartment of Chemistry, Scripps Research, Jupiter, FL 33458, USADepartment of Molecular Medicine, Scripps Research, Jupiter, FL 33458, USAMeprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.https://www.mdpi.com/1424-8247/14/3/197meprin αmeprin βzinc metalloproteinasemedicinal chemistryprobe development |
| spellingShingle | Chao Wang Juan Diez Hajeung Park Christoph Becker-Pauly Gregg B. Fields Timothy P. Spicer Louis D. Scampavia Dmitriy Minond Thomas D. Bannister Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) Pharmaceuticals meprin α meprin β zinc metalloproteinase medicinal chemistry probe development |
| title | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
| title_full | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
| title_fullStr | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
| title_full_unstemmed | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
| title_short | Discovery and Optimization of Selective Inhibitors of Meprin α (Part II) |
| title_sort | discovery and optimization of selective inhibitors of meprin α part ii |
| topic | meprin α meprin β zinc metalloproteinase medicinal chemistry probe development |
| url | https://www.mdpi.com/1424-8247/14/3/197 |
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