Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules
Current drug development strategies that target either enzymatic or receptor proteins for which specific small molecule ligands can be designed for modulation, result in a large portion of the proteome being overlooked as undruggable. The recruitment of natural degradation cascades for targeted prot...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-09-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/24/18/3272 |
| _version_ | 1818425662158929920 |
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| author | Alexandré Delport Raymond Hewer |
| author_facet | Alexandré Delport Raymond Hewer |
| author_sort | Alexandré Delport |
| collection | DOAJ |
| description | Current drug development strategies that target either enzymatic or receptor proteins for which specific small molecule ligands can be designed for modulation, result in a large portion of the proteome being overlooked as undruggable. The recruitment of natural degradation cascades for targeted protein removal using heterobifunctional molecules (or degraders) provides a likely avenue to expand the druggable proteome. In this review, we discuss the use of this drug development strategy in relation to degradation cascade-recruiting mechanisms and successfully targeted disease-related proteins. Essential characteristics to be considered in degrader design are deliberated upon and future development challenges mentioned. |
| first_indexed | 2024-12-14T14:17:30Z |
| format | Article |
| id | doaj.art-8459efa42a2b4d12a5d521d3652cd2f2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-14T14:17:30Z |
| publishDate | 2019-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8459efa42a2b4d12a5d521d3652cd2f22022-12-21T22:58:10ZengMDPI AGMolecules1420-30492019-09-012418327210.3390/molecules24183272molecules24183272Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional MoleculesAlexandré Delport0Raymond Hewer1Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg 3201, South AfricaDiscipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Pietermaritzburg 3201, South AfricaCurrent drug development strategies that target either enzymatic or receptor proteins for which specific small molecule ligands can be designed for modulation, result in a large portion of the proteome being overlooked as undruggable. The recruitment of natural degradation cascades for targeted protein removal using heterobifunctional molecules (or degraders) provides a likely avenue to expand the druggable proteome. In this review, we discuss the use of this drug development strategy in relation to degradation cascade-recruiting mechanisms and successfully targeted disease-related proteins. Essential characteristics to be considered in degrader design are deliberated upon and future development challenges mentioned.https://www.mdpi.com/1420-3049/24/18/3272PROTACsSNIPERstargeted protein degradationdrug development |
| spellingShingle | Alexandré Delport Raymond Hewer Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules Molecules PROTACs SNIPERs targeted protein degradation drug development |
| title | Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules |
| title_full | Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules |
| title_fullStr | Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules |
| title_full_unstemmed | Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules |
| title_short | Inducing the Degradation of Disease-Related Proteins Using Heterobifunctional Molecules |
| title_sort | inducing the degradation of disease related proteins using heterobifunctional molecules |
| topic | PROTACs SNIPERs targeted protein degradation drug development |
| url | https://www.mdpi.com/1420-3049/24/18/3272 |
| work_keys_str_mv | AT alexandredelport inducingthedegradationofdiseaserelatedproteinsusingheterobifunctionalmolecules AT raymondhewer inducingthedegradationofdiseaserelatedproteinsusingheterobifunctionalmolecules |