Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs
New therapeutic modalities are needed to address the problem of pathological but undruggable proteins. One possible approach is the induction of protein degradation by chimeric drugs composed of a ubiquitin ligase (E3) ligand coupled to a ligand for the target protein. This article reviews chimeric...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-04-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/4/74 |
| _version_ | 1797570007387865088 |
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| author | Minoru Ishikawa Shusuke Tomoshige Yosuke Demizu Mikihiko Naito |
| author_facet | Minoru Ishikawa Shusuke Tomoshige Yosuke Demizu Mikihiko Naito |
| author_sort | Minoru Ishikawa |
| collection | DOAJ |
| description | New therapeutic modalities are needed to address the problem of pathological but undruggable proteins. One possible approach is the induction of protein degradation by chimeric drugs composed of a ubiquitin ligase (E3) ligand coupled to a ligand for the target protein. This article reviews chimeric drugs that decrease the level of specific proteins such as proteolysis targeting chimeric molecules (PROTACs) and specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs), which target proteins for proteasome-mediated degradation. We cover strategies for increasing the degradation activity induced by small molecules, and their scope for application to undruggable proteins. |
| first_indexed | 2024-03-10T20:19:07Z |
| format | Article |
| id | doaj.art-3d1ef3dbc2024116988486ee8de2326f |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:19:07Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-3d1ef3dbc2024116988486ee8de2326f2023-11-19T22:16:45ZengMDPI AGPharmaceuticals1424-82472020-04-011347410.3390/ph13040074Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERsMinoru Ishikawa0Shusuke Tomoshige1Yosuke Demizu2Mikihiko Naito3Graduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanGraduate School of Life Sciences, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, JapanDivision of Organic Chemistry, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki, Kanagawa 210-9501, JapanDivision of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, 3-25-26, Tonomachi, Kawasaki, Kanagawa 210-9501, JapanNew therapeutic modalities are needed to address the problem of pathological but undruggable proteins. One possible approach is the induction of protein degradation by chimeric drugs composed of a ubiquitin ligase (E3) ligand coupled to a ligand for the target protein. This article reviews chimeric drugs that decrease the level of specific proteins such as proteolysis targeting chimeric molecules (PROTACs) and specific and nongenetic inhibitor of apoptosis protein (IAP)-dependent protein erasers (SNIPERs), which target proteins for proteasome-mediated degradation. We cover strategies for increasing the degradation activity induced by small molecules, and their scope for application to undruggable proteins.https://www.mdpi.com/1424-8247/13/4/74PROTACsSNIPERschemical protein degradation |
| spellingShingle | Minoru Ishikawa Shusuke Tomoshige Yosuke Demizu Mikihiko Naito Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs Pharmaceuticals PROTACs SNIPERs chemical protein degradation |
| title | Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs |
| title_full | Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs |
| title_fullStr | Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs |
| title_full_unstemmed | Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs |
| title_short | Selective Degradation of Target Proteins by Chimeric Small-Molecular Drugs, PROTACs and SNIPERs |
| title_sort | selective degradation of target proteins by chimeric small molecular drugs protacs and snipers |
| topic | PROTACs SNIPERs chemical protein degradation |
| url | https://www.mdpi.com/1424-8247/13/4/74 |
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