Molecular screening and docking analysis of LMTK3 and AKT1 combined inhibitors
| Autor: | El Amri Hamid, Lakhlili Wiame, Loubna Allam, Ghrifi Fatima, Ibrahim Azeddine |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
AKT1
Virtual screening 0301 basic medicine Drug Quantitative structure–activity relationship ATP-inhibitors QSAR Chemistry media_common.quotation_subject Biological activity General Medicine Drug resistance Computational biology Hypothesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine LMTK3 Docking (molecular) 030220 oncology & carcinogenesis embryonic structures Protein kinase B media_common ADME |
| Zdroj: | Bioinformation |
| ISSN: | 0973-2063 0973-8894 |
| DOI: | 10.6026/97320630014499 |
| Popis: | The abnormal activation of AKT/mTOR signaling pathway and overexpression of LMTK3, are the main factors involved in the generation of drug resistance. Therefore, the use of computer-aided drug design in the inhibitors discovery offers an advantage to provide new candidates for the treatment of this resistance. We realised the virtual screening and molecular docking of AKT1 and LMTK3 proteins by the Dockblaster server. In addition, with abundance of candidates under development for AKT1 kinase, we have also conducted a Quantitative Structure-Activity Relationship (QSAR) study based on these compounds, in order to design more active compounds and predict their activity for development of a new inhibitor of AKT1. QSAR tests were performed for AKT1 using the Partial Least Squares method with a correlation coefficient of R2=0.8062 and a cross-validation of q2=0.6995. This test has selected five compounds as competitive inhibitors-AKT1-ATP with a better biological activities. In parallel the molecular screening has selected five other compounds as competitive ATP-inhibitors of LMTK3. One of them is a common inhibitor with AKT1, and it is marketed as a moderate to severe pain therapy. The ADME predictions confirmed the inhibitors pharmacological activity of these compounds for potential consideration as drug candidates. |
| Databáze: | OpenAIRE |
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