An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions
Human protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically w...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/24/17504 |
| _version_ | 1797380661593505792 |
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| author | Mulate Zerihun Samuel J. S. Rubin Shmuel Silnitsky Nir Qvit |
| author_facet | Mulate Zerihun Samuel J. S. Rubin Shmuel Silnitsky Nir Qvit |
| author_sort | Mulate Zerihun |
| collection | DOAJ |
| description | Human protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP-binding pocket. As a result, these compounds are often poorly selective and highly toxic. Part I of this series reviews the role of PKC isoforms in various human diseases, featuring cancer and cardiovascular disease, as well as translational examples of PKC modulation applied to human health and disease. In the present Part II, we discuss alternative allosteric binding mechanisms for targeting PKC, as well as novel drug platforms, such as modified peptides. A major goal is to design protein kinase modulators with enhanced selectivity and improved pharmacological properties. To this end, we use molecular docking analysis to predict the mechanisms of action for inhibitor–kinase interactions that can facilitate the development of next-generation PKC modulators. |
| first_indexed | 2024-03-08T20:40:28Z |
| format | Article |
| id | doaj.art-0abe09b6c29349a490490444dfd39ec9 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T20:40:28Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0abe09b6c29349a490490444dfd39ec92023-12-22T14:14:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-12-0124241750410.3390/ijms242417504An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein InteractionsMulate Zerihun0Samuel J. S. Rubin1Shmuel Silnitsky2Nir Qvit3The Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, P.O. Box 1589, Safed 1311502, IsraelDepartment of Medicine, School of Medicine, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USAThe Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, P.O. Box 1589, Safed 1311502, IsraelThe Azrieli Faculty of Medicine in the Galilee, Bar-Ilan University, Henrietta Szold St. 8, P.O. Box 1589, Safed 1311502, IsraelHuman protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP-binding pocket. As a result, these compounds are often poorly selective and highly toxic. Part I of this series reviews the role of PKC isoforms in various human diseases, featuring cancer and cardiovascular disease, as well as translational examples of PKC modulation applied to human health and disease. In the present Part II, we discuss alternative allosteric binding mechanisms for targeting PKC, as well as novel drug platforms, such as modified peptides. A major goal is to design protein kinase modulators with enhanced selectivity and improved pharmacological properties. To this end, we use molecular docking analysis to predict the mechanisms of action for inhibitor–kinase interactions that can facilitate the development of next-generation PKC modulators.https://www.mdpi.com/1422-0067/24/24/17504kinasesprotein kinase Callostericpeptidespeptidomimeticsmodified peptides |
| spellingShingle | Mulate Zerihun Samuel J. S. Rubin Shmuel Silnitsky Nir Qvit An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions International Journal of Molecular Sciences kinases protein kinase C allosteric peptides peptidomimetics modified peptides |
| title | An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions |
| title_full | An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions |
| title_fullStr | An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions |
| title_full_unstemmed | An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions |
| title_short | An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions |
| title_sort | update on protein kinases as therapeutic targets part ii peptides as allosteric protein kinase c modulators targeting protein protein interactions |
| topic | kinases protein kinase C allosteric peptides peptidomimetics modified peptides |
| url | https://www.mdpi.com/1422-0067/24/24/17504 |
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