Predicting the effects of effective compounds on the interleukin-6 induced inflammation pathway on existing colon cancer related receptors

Abstract

Introduction: Interleukin-6 is an inflammatory cytokine that affects various colorectal cancer related pathways. Discovery of compounds with the capability of targeting Interleukin-6 is one of the treatment development strategies for colorectal cancer. Objective: Predicting the colorectal cancer associated targets that could be targeted with the inhibitors of the interleukin-6 and its receptor pathway Methods: Targets related to IL6 pathway were selected using the KEGG database. The related compounds were extracted from Chembl25 and the Tanimoto similarity index was calculated using Morgan fingerprints. The paired targets for each compound was predicted. Molecular docking methods were used to investigate the interaction of the selected compounds with the predicted targets. To conduct the study, a systematic data method was developed using the KNIME platform. The required data server was also created using MYSQL software and the Chembl25 database, which allows the platform to be used offline. Results: At the beginning from KEGG database, 76 targets and 44946 compounds selected. After application of rule-based filters, 246 compounds for 43 targets in 74 pairs selected. By examining the importance of target pairs, GSK3-AKT1, GSK3-JAK1, STAT3-AKT1 and mTOR-AKT1 target pairs were selected. The interaction of one inhibitor compound for each pair was investigated by molecular docking method in comparison with the available inhibitor compounds and the results were discussed. Conclusion: Using the developed method in this study, the effective compounds on the pair of targets with synergistic effect in colorectal cancer were identified. The developed data mining has made it possible to conduct studies with many targets and ligands in a total time of 20 minutes. It also has accelerated the analysis of the results. The results of this method can be used for target identification and lead compound finding purposes.