New computational studies to support cyclin-dependent kinase 9 inhibitor screening and design
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Tartalom: https://www.aph-hsps.hu/acta/index.php/aph/article/view/8
Archívum: Acta Pharmaceutica
Gyűjtemény: Original Research Articles
Cím:
New computational studies to support cyclin-dependent kinase 9 inhibitor screening and design
Létrehozó:
Fábián, Márk
Balogh, Balázs
Czudor, Zsófia
Őrfi, László
Kiadó:
Hungarian Society for Pharmaceutical Sciences
Dátum:
2019-04-09
Téma:
CDK9 inhibitor, docking, QSAR, pharmacophore model
Kinase inhibitor research
Tartalmi leírás:
Aims: Cyclin-dependent kinase 9 (CDK9) plays a major role in the regulation of transcription. Its overexpression -which occurs in several types of cancer- increases the levels of certain antiapoptotic proteins that can lead to tumorigenesis, therefore the identification of new, more potent and more selective inhibitors is essential. Methods: In this study we present a computational approach, which can facilitate lead selection and optimization. Results: First, a pharmacophore hypothesis based on the active compounds has been developed to identify the key features for the ligand-target interaction. This was followed by the docking of the compounds into the active site of CDK9, the poses and interactions with the amino acids were compared with those of the co-crystallized ligand. The mode of their binding further explained the characteristics of these inhibitors while the docking scores can be a factor in the selection of active compounds in the future. Finally, a field-based QSAR model was also created, to predict the activity of inhibitor candidates. Conclusion: With our current work we deepened our knowledge about the interactions between CDK9 and its inhibitors, which can contribute to the discovery of novel CDK9 inhibitors.  
Nyelv:
angol
Típus:
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Formátum:
application/pdf
Azonosító:
Forrás:
Acta Pharmaceutica Hungarica; Vol. 89 No. 1 (2019); 31-38
1587-1495
0001-6659
Kapcsolat:
Létrehozó:
Copyright (c) 2019 Acta Pharmaceutica Hungarica