The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | http://www.mdpi.com/1424-8247/10/1/26 |
| _version_ | 1819063364713709568 |
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| author | Giorgio Cozza |
| author_facet | Giorgio Cozza |
| author_sort | Giorgio Cozza |
| collection | DOAJ |
| description | Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by “trial and error testing”. In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range. The screening of big chemical libraries and the optimization of hit compounds by Structure Based Drug Design (SBDD) provide telling examples of a fruitful application of rational drug design to the development of CK2 inhibitors. Ligand Based Drug Design (LBDD) models have been also applied to CK2 drug discovery, however they were mainly focused on methodology improvements rather than being critical for de novo design and optimization. This manuscript provides detailed description of in silico methodologies whose applications to the design and development of CK2 inhibitors proved successful and promising. |
| first_indexed | 2024-12-21T15:13:30Z |
| format | Article |
| id | doaj.art-ab8653651950441dae103f07dce5783d |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-12-21T15:13:30Z |
| publishDate | 2017-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ab8653651950441dae103f07dce5783d2022-12-21T18:59:14ZengMDPI AGPharmaceuticals1424-82472017-02-011012610.3390/ph10010026ph10010026The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug DesignGiorgio Cozza0Department of Molecular Medicine, University of Padova; 35131, Padova, ItalyCasein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by “trial and error testing”. In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range. The screening of big chemical libraries and the optimization of hit compounds by Structure Based Drug Design (SBDD) provide telling examples of a fruitful application of rational drug design to the development of CK2 inhibitors. Ligand Based Drug Design (LBDD) models have been also applied to CK2 drug discovery, however they were mainly focused on methodology improvements rather than being critical for de novo design and optimization. This manuscript provides detailed description of in silico methodologies whose applications to the design and development of CK2 inhibitors proved successful and promising.http://www.mdpi.com/1424-8247/10/1/26CK2inhibitorsstructure based drug designligand based drug designcancerhit optimization |
| spellingShingle | Giorgio Cozza The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design Pharmaceuticals CK2 inhibitors structure based drug design ligand based drug design cancer hit optimization |
| title | The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design |
| title_full | The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design |
| title_fullStr | The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design |
| title_full_unstemmed | The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design |
| title_short | The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design |
| title_sort | development of ck2 inhibitors from traditional pharmacology to in silico rational drug design |
| topic | CK2 inhibitors structure based drug design ligand based drug design cancer hit optimization |
| url | http://www.mdpi.com/1424-8247/10/1/26 |
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