Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases
Cyclin-dependent kinases (CDKs) play diverse and critical roles in normal cells and may be exploited as targets in cancer therapeutic strategies. CDK4 inhibitors are currently approved for treatment in advanced breast cancer. This success has led to continued pursuit of targeting other CDKs. One cha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/4/519 |
| _version_ | 1797603989856976896 |
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| author | Mark Klein |
| author_facet | Mark Klein |
| author_sort | Mark Klein |
| collection | DOAJ |
| description | Cyclin-dependent kinases (CDKs) play diverse and critical roles in normal cells and may be exploited as targets in cancer therapeutic strategies. CDK4 inhibitors are currently approved for treatment in advanced breast cancer. This success has led to continued pursuit of targeting other CDKs. One challenge has been in the development of inhibitors that are highly selective for individual CDKs as the ATP-binding site is highly conserved across this family of proteins. Protein-protein interactions (PPI) tend to have less conservation amongst different proteins, even within protein families, making targeting PPI an attractive approach to improving drug selectivity. However, PPI can be challenging to target due to structural and physicochemical features of these interactions. A review of the literature specific to studies focused on targeting PPI involving CDKs 2, 4, 5, and 9 was conducted and is presented here. Promising lead molecules to target select CDKs have been discovered. None of the lead molecules discovered have led to FDA approval; however, the studies covered in this review lay the foundation for further discovery and develop of PPI inhibitors for CDKs. |
| first_indexed | 2024-03-11T04:39:50Z |
| format | Article |
| id | doaj.art-e6b1af4d61864470a34cb9bb3647473f |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T04:39:50Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-e6b1af4d61864470a34cb9bb3647473f2023-11-17T20:50:05ZengMDPI AGPharmaceuticals1424-82472023-03-0116451910.3390/ph16040519Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent KinasesMark Klein0Hematology/Oncology Section, Primary Care Service Line, Minneapolis VA Healthcare System, Minneapolis, MN 55417, USACyclin-dependent kinases (CDKs) play diverse and critical roles in normal cells and may be exploited as targets in cancer therapeutic strategies. CDK4 inhibitors are currently approved for treatment in advanced breast cancer. This success has led to continued pursuit of targeting other CDKs. One challenge has been in the development of inhibitors that are highly selective for individual CDKs as the ATP-binding site is highly conserved across this family of proteins. Protein-protein interactions (PPI) tend to have less conservation amongst different proteins, even within protein families, making targeting PPI an attractive approach to improving drug selectivity. However, PPI can be challenging to target due to structural and physicochemical features of these interactions. A review of the literature specific to studies focused on targeting PPI involving CDKs 2, 4, 5, and 9 was conducted and is presented here. Promising lead molecules to target select CDKs have been discovered. None of the lead molecules discovered have led to FDA approval; however, the studies covered in this review lay the foundation for further discovery and develop of PPI inhibitors for CDKs.https://www.mdpi.com/1424-8247/16/4/519protein-protein interaction inhibitorcyclin-dependent kinasecyclinneoplasm |
| spellingShingle | Mark Klein Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases Pharmaceuticals protein-protein interaction inhibitor cyclin-dependent kinase cyclin neoplasm |
| title | Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases |
| title_full | Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases |
| title_fullStr | Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases |
| title_full_unstemmed | Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases |
| title_short | Targeting Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases |
| title_sort | targeting protein protein interactions to inhibit cyclin dependent kinases |
| topic | protein-protein interaction inhibitor cyclin-dependent kinase cyclin neoplasm |
| url | https://www.mdpi.com/1424-8247/16/4/519 |
| work_keys_str_mv | AT markklein targetingproteinproteininteractionstoinhibitcyclindependentkinases |