Target prediction for the AKT inhibitors in the inflammatory pathway of colorectal cancer using similarity-based methods from Chembl۲۵ database

The pathway of Interleukin-۶ (IL۶) as one of the inflammatory cytokines that its contribution to colorectalcancer pathology is known, was investigated to extract the related target list. AKT is a serine/threonine kinaseprotein which can stimulate a large different extracellular factor. Synergestic effect of simultaneous inhibitionAKT and some targets in the pathway of IL۶ have been reported. In this study we used a similarity-basedmethod for the target prediction for AKT inhibitors from IL۶ pathway. The target list was extracted from theKEGG database and Chembl۲۵ was used to extract the inhibitors. The Morgan fingerprints was calculatedusing RDKit that was implemented in a Knime platform. Tanimoto similarity index was calculated anddifferent thresholds were used to indicate similarity. The predicted targets for AKT inhibitors were GSK۳β,PDKI۱, PIM۱, mTOR, JAK۱, TIE-۲ and STAT۳. The literature and databases survey indicated the availableevidences for the inhibition of the predicted targets. As the synergestic effect of AKT-STAT۳ has beenreported earlier. The pyrimidine compound with the predicted inhibition of STAT۳ was further evaluatedusing molecular docking. Docking simulation was done by AutoDock software. The results indicated that theappropriate interaction between AKT and selected compound. Binding energy value is -۸.۳۴ Kcal/molbetween them.

Keywords:

Interleukin-۶ , Colorectal Cancer , Inflammation , Database , Molecular Docking