Abstract 4937: Potential therapeutic targets with anti-inflammatory activity spectrum(COX-2/PGE2) of compounds associated with anti-cancer activityagainst oral and colorectal cancers

Abstract

Abstract Introduction: COX-2 and PGE2 are prevalent inflammatory cytokines that exert influence on several cancer-related pathways throughout the gastrointestinal tract, spanning from oral cancers to colorectal cancers. One of the tactics being developed for the treatment of oral and colorectal malignancies is the identification of drugs that can selectively target receptors associated with COX-2 and PGE2. Materials and Methods: The objective was to identify potential therapeutic targets for oral cancer and colorectal cancer, specifically focusing on drugs that act as inhibitors or antagonists of the COX2/PGE2 pathway and its related receptor. A method for systematic data mining was created with a total of 32 targets associated with the COX-2/PGE2 pathway which were identified using the KEGG database. These targets were shown to be linked to both the oral cancer pathway and the colorectal cancer pathway. The compounds of interest were obtained from the Chembl25 database and their similarity was assessed using the Tanimoto similarity index, which was generated based on the Morgan fingerprints. The study employed molecular docking techniques to examine the interaction between the chosen drugs and the anticipated targets. A systematic data mining approach and computational methodology were devised utilizing the KNIME platform. Results: A total of 16,900 compounds were extracted for a set of 32 targets. Following the implementation of rule-based filters, the number of compounds was reduced to 13,800. The compounds that have a similarity index greater than 0.7 were chosen for inclusion in final analysis. Among various targets examined, empirical evidence was found to support the inhibition of expected target for PI-3 kinase-mTOR, GSK-3CD1, GSK3-AKT and PI3kinase-AKT pair. However, no evidence was found to support the inhibition of GSK3-Ikappa B-kinase. In order to examine the likelihood of the compound's interaction with anticipated target, molecular docking was employed to explore the interaction of one inhibitor compound for each pair. This investigation was conducted in contrast to the existing inhibitor compound and the subsequent findings were analyzed and discussed. Conclusion: The implemented data mining technique has demonstrated a notable decrease in the duration needed for comparable investigations, enabling the execution of experiments including numerous targets and a substantial number of ligands within a cumulative timeframe of 30 minutes. The findings of this study have the potential to be utilized in the identification of targets and the discovery of lead compounds for the purpose of managing oral as well as colorectal malignancies. Citation Format: Saravanan Sampoornam Pape. Potential therapeutic targets with anti-inflammatory activity spectrum(COX-2/PGE2) of compounds associated with anti-cancer activityagainst oral and colorectal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4937.