Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors
Conventional small-molecule drugs (SMDs) are compounds characterized by low molecular weight, high cell permeability, and high selectivity. In clinical translation, SMDs are regarded as good candidates for oral drug formulation. SMD inhibitors play an important role in cancer treatment; however, res...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-04-01
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| Series: | Technology in Cancer Research & Treatment |
| Online Access: | https://doi.org/10.1177/15330338221095950 |
| _version_ | 1817991325776084992 |
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| author | Mengyuan Dai PhD Sridhar Radhakrishnan PhD Rui Li PhD Ruirong Tan PhD Kuo Yan PhD Gang Fan PhD Miao Liu PhD |
| author_facet | Mengyuan Dai PhD Sridhar Radhakrishnan PhD Rui Li PhD Ruirong Tan PhD Kuo Yan PhD Gang Fan PhD Miao Liu PhD |
| author_sort | Mengyuan Dai PhD |
| collection | DOAJ |
| description | Conventional small-molecule drugs (SMDs) are compounds characterized by low molecular weight, high cell permeability, and high selectivity. In clinical translation, SMDs are regarded as good candidates for oral drug formulation. SMD inhibitors play an important role in cancer treatment; however, resistance and low effectiveness have been major bottlenecks in clinical application. Generally, only 20% of cell proteins can potentially be targeted and have been developed as SMDs; thus, some types of tumor targets are considered “undruggable.” Among these are transcription factors (TFs), an important class of proteins that regulate the occurrence, formation, and development of tumors. It is difficult for SMDs and macromolecular drugs to identify bioactive sites in TFs and hence for use as pharmacological inhibitors in targeting TF proteins. For this reason, technologies that enable targeted protein degradation, such as proteolysis-targeting chimera or molecular glues, could serve as a potential tool to solve these conundrums. |
| first_indexed | 2024-04-14T01:10:54Z |
| format | Article |
| id | doaj.art-1c4f5a35d85c4a70b7413ff9f7493fc3 |
| institution | Directory Open Access Journal |
| issn | 1533-0338 |
| language | English |
| last_indexed | 2024-04-14T01:10:54Z |
| publishDate | 2022-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Technology in Cancer Research & Treatment |
| spelling | doaj.art-1c4f5a35d85c4a70b7413ff9f7493fc32022-12-22T02:21:02ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382022-04-012110.1177/15330338221095950Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription FactorsMengyuan Dai PhD0Sridhar Radhakrishnan PhD1Rui Li PhD2Ruirong Tan PhD3Kuo Yan PhD4Gang Fan PhD5Miao Liu PhD6 Department of Gynecological Oncology, , Wuhan, China Cancer Science Institute of Singapore, , Singapore, Singapore Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China Translational Chinese Medicine Key Laboratory of Sichuan Province, Sichuan Institute for Translational Chinese Medicine, , Chengdu, China Institute of Cell and Neurobiology, Charité Medical University, Berlin, Germany , Shenzhen, China Department of Pathology, , Harvard Medical School, Boston, MA, USAConventional small-molecule drugs (SMDs) are compounds characterized by low molecular weight, high cell permeability, and high selectivity. In clinical translation, SMDs are regarded as good candidates for oral drug formulation. SMD inhibitors play an important role in cancer treatment; however, resistance and low effectiveness have been major bottlenecks in clinical application. Generally, only 20% of cell proteins can potentially be targeted and have been developed as SMDs; thus, some types of tumor targets are considered “undruggable.” Among these are transcription factors (TFs), an important class of proteins that regulate the occurrence, formation, and development of tumors. It is difficult for SMDs and macromolecular drugs to identify bioactive sites in TFs and hence for use as pharmacological inhibitors in targeting TF proteins. For this reason, technologies that enable targeted protein degradation, such as proteolysis-targeting chimera or molecular glues, could serve as a potential tool to solve these conundrums.https://doi.org/10.1177/15330338221095950 |
| spellingShingle | Mengyuan Dai PhD Sridhar Radhakrishnan PhD Rui Li PhD Ruirong Tan PhD Kuo Yan PhD Gang Fan PhD Miao Liu PhD Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors Technology in Cancer Research & Treatment |
| title | Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors |
| title_full | Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors |
| title_fullStr | Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors |
| title_full_unstemmed | Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors |
| title_short | Targeted Protein Degradation: An Important Tool for Drug Discovery for “Undruggable” Tumor Transcription Factors |
| title_sort | targeted protein degradation an important tool for drug discovery for undruggable tumor transcription factors |
| url | https://doi.org/10.1177/15330338221095950 |
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