Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System
Bivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the prot...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-11-01
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| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/23/8119 |
| _version_ | 1797462754897952768 |
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| author | Sridhar Radhakrishnan Oskar Hoff Markus K. Muellner |
| author_facet | Sridhar Radhakrishnan Oskar Hoff Markus K. Muellner |
| author_sort | Sridhar Radhakrishnan |
| collection | DOAJ |
| description | Bivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the proteasome via ubiquitination. In this review we provide an overview of the current state of E3 ligases used in targeted protein degradation, their respective ligands as well as challenges and opportunities that present themselves with these compounds. |
| first_indexed | 2024-03-09T17:41:09Z |
| format | Article |
| id | doaj.art-f16c15a3f3504d74a93293d930042935 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:41:09Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f16c15a3f3504d74a93293d9300429352023-11-24T11:36:55ZengMDPI AGMolecules1420-30492022-11-012723811910.3390/molecules27238119Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal SystemSridhar Radhakrishnan0Oskar Hoff1Markus K. Muellner2Celeris Therapeutics, Inc., Menlo Park, CA 94025, USACeleris Therapeutics, Inc., Menlo Park, CA 94025, USACeleris Therapeutics, Inc., Menlo Park, CA 94025, USABivalent proximity-inducing compounds represent a novel class of small molecule therapeutics with exciting potential and new challenges. The most prominent examples of such compounds are utilized in targeted protein degradation where E3 ligases are hijacked to recruit a substrate protein to the proteasome via ubiquitination. In this review we provide an overview of the current state of E3 ligases used in targeted protein degradation, their respective ligands as well as challenges and opportunities that present themselves with these compounds.https://www.mdpi.com/1420-3049/27/23/8119PROTACPICtargeted protein degradationproximity-inducing compoundE3 recruiterubiquitination |
| spellingShingle | Sridhar Radhakrishnan Oskar Hoff Markus K. Muellner Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System Molecules PROTAC PIC targeted protein degradation proximity-inducing compound E3 recruiter ubiquitination |
| title | Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System |
| title_full | Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System |
| title_fullStr | Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System |
| title_full_unstemmed | Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System |
| title_short | Current Challenges in Small Molecule Proximity-Inducing Compound Development for Targeted Protein Degradation Using the Ubiquitin Proteasomal System |
| title_sort | current challenges in small molecule proximity inducing compound development for targeted protein degradation using the ubiquitin proteasomal system |
| topic | PROTAC PIC targeted protein degradation proximity-inducing compound E3 recruiter ubiquitination |
| url | https://www.mdpi.com/1420-3049/27/23/8119 |
| work_keys_str_mv | AT sridharradhakrishnan currentchallengesinsmallmoleculeproximityinducingcompounddevelopmentfortargetedproteindegradationusingtheubiquitinproteasomalsystem AT oskarhoff currentchallengesinsmallmoleculeproximityinducingcompounddevelopmentfortargetedproteindegradationusingtheubiquitinproteasomalsystem AT markuskmuellner currentchallengesinsmallmoleculeproximityinducingcompounddevelopmentfortargetedproteindegradationusingtheubiquitinproteasomalsystem |