|
Title |
Molecular screening and docking analysis of LMTK3 and AKT1 combined inhibitors
|
|
Authors |
Loubna Allam1,2*, Ghrifi Fatima1, Lakhlili Wiame1, Hamid El Amri2 and Azeddine Ibrahimi1
|
|
Affiliation |
1Biotechnology Laboratory (Medbiotech), BioInova Research center, Rabat Medical and Pharmacy School, MedBiotech Center, Mohammed V University in Rabat, Rabat, 10000, Morroco; 2Genetics Laboratory of Royal Gendarmery, Rabat, Morocco.
|
|
|
Loubna Allam - Email : allamloubna09@gmail.com; *Corresponding author
|
|
Article Type |
Hypothesis
|
|
Date |
Recieved October 30, 2018 ; Revised November 20, 2018 ; Accepted November 22, 2018, Published December 9, 2018
|
|
Abstract |
The abnormal activation of AKT/mTOR signaling pathway and over expression 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.
|
|
Keywords |
AKT1, QSAR, LMTK3, Virtual screening, ATP-inhibitors.
|
|
Citation |
Allam et al. Bioinformation 14(9) 499-503 (2018)
|
|
Edited by |
P Kangueane
|
|
ISSN |
0973-2063
|
|
Publisher |
|
|
License |
This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.
|