Current Status of Oligonucleotide-Based Protein Degraders
Transcription factors (TFs) and RNA-binding proteins (RBPs) have long been considered undruggable, mainly because they lack ligand-binding sites and are equipped with flat and narrow protein surfaces. Protein-specific oligonucleotides have been harnessed to target these proteins with some satisfacto...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/3/765 |
| _version_ | 1797609555171999744 |
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| author | Po-Chang Shih Miyako Naganuma Yosuke Demizu Mikihiko Naito |
| author_facet | Po-Chang Shih Miyako Naganuma Yosuke Demizu Mikihiko Naito |
| author_sort | Po-Chang Shih |
| collection | DOAJ |
| description | Transcription factors (TFs) and RNA-binding proteins (RBPs) have long been considered undruggable, mainly because they lack ligand-binding sites and are equipped with flat and narrow protein surfaces. Protein-specific oligonucleotides have been harnessed to target these proteins with some satisfactory preclinical results. The emerging proteolysis-targeting chimera (PROTAC) technology is no exception, utilizing protein-specific oligonucleotides as warheads to target TFs and RBPs. In addition, proteolysis by proteases is another type of protein degradation. In this review article, we discuss the current status of oligonucleotide-based protein degraders that are dependent either on the ubiquitin–proteasome system or a protease, providing a reference for the future development of degraders. |
| first_indexed | 2024-03-11T06:01:59Z |
| format | Article |
| id | doaj.art-39963b9a532246ed9ff51139ba4749c6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T06:01:59Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-39963b9a532246ed9ff51139ba4749c62023-11-17T13:14:04ZengMDPI AGPharmaceutics1999-49232023-02-0115376510.3390/pharmaceutics15030765Current Status of Oligonucleotide-Based Protein DegradersPo-Chang Shih0Miyako Naganuma1Yosuke Demizu2Mikihiko Naito3Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanNational Institute of Health Sciences, Kawasaki 210-9501, JapanGraduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, JapanTranscription factors (TFs) and RNA-binding proteins (RBPs) have long been considered undruggable, mainly because they lack ligand-binding sites and are equipped with flat and narrow protein surfaces. Protein-specific oligonucleotides have been harnessed to target these proteins with some satisfactory preclinical results. The emerging proteolysis-targeting chimera (PROTAC) technology is no exception, utilizing protein-specific oligonucleotides as warheads to target TFs and RBPs. In addition, proteolysis by proteases is another type of protein degradation. In this review article, we discuss the current status of oligonucleotide-based protein degraders that are dependent either on the ubiquitin–proteasome system or a protease, providing a reference for the future development of degraders.https://www.mdpi.com/1999-4923/15/3/765degrader therapeuticstargeted protein degradationPROTACSNIPERnucleic acidsproteases |
| spellingShingle | Po-Chang Shih Miyako Naganuma Yosuke Demizu Mikihiko Naito Current Status of Oligonucleotide-Based Protein Degraders Pharmaceutics degrader therapeutics targeted protein degradation PROTAC SNIPER nucleic acids proteases |
| title | Current Status of Oligonucleotide-Based Protein Degraders |
| title_full | Current Status of Oligonucleotide-Based Protein Degraders |
| title_fullStr | Current Status of Oligonucleotide-Based Protein Degraders |
| title_full_unstemmed | Current Status of Oligonucleotide-Based Protein Degraders |
| title_short | Current Status of Oligonucleotide-Based Protein Degraders |
| title_sort | current status of oligonucleotide based protein degraders |
| topic | degrader therapeutics targeted protein degradation PROTAC SNIPER nucleic acids proteases |
| url | https://www.mdpi.com/1999-4923/15/3/765 |
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