1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Target prediction for the AKT inhibitors in the inflammatory pathway of colorectal cancer using similarity-based methods from Chembl25 database
Paper ID : 1330-ICB10
Authors:
Alireza Ghavami1, Andreas Bender2, Mostafa Zakariazadeh3, Somaieh Soltani *1
1Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2Department of Chemistry, Centre for Molecular Informatics, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
3Department of Biology, Faculty of Sciences, Payame Noor University, Tehran, Iran
Abstract:
The pathway of Interleukin-6 (IL6) as one of the inflammatory cytokines that its contribution to colorectal cancer pathology is known, was investigated to extract the related target list. AKT is a serine/threonine kinase protein which can stimulate a large different extracellular factor. Synergestic effect of simultaneous inhibition AKT and some targets in the pathway of IL6 have been reported. In this study we used a similarity-based method for the target prediction for AKT inhibitors from IL6 pathway. The target list was extracted from the KEGG database and Chembl25 was used to extract the inhibitors. The Morgan fingerprints was calculated using RDKit that was implemented in a Knime platform. Tanimoto similarity index was calculated and different thresholds were used to indicate similarity. The predicted targets for AKT inhibitors were GSK3β, PDKI1, PIM1, mTOR, JAK1, TIE-2 and STAT3. The literature and databases survey indicated the available evidences for the inhibition of the predicted targets. As the synergestic effect of AKT-STAT3 has been reported earlier. The pyrimidine compound with the predicted inhibition of STAT3 was further evaluated using molecular docking. Docking simulation was done by AutoDock software. The results indicated that the appropriate interaction between AKT and selected compound. Binding energy value is -8.34 Kcal/mol between them.
Keywords:
Interleukin-6; Colorectal Cancer; Inflammation; Database; Molecular Docking
Status : Paper Accepted (Poster Presentation)