Poster Presenter

Prediction of MEK Inhibition and Oral Bioavailability of Novel Isothiazole Derivatives using in Silico Techniques
Georgia Melagraki, Antreas Afantitis, Panayiotis A. Koutentis, and George Kollias
Cyprus


A goal of modern cancer therapy is to identify molecules in signal transduction pathways that affect cell growth, and particularly those that cause a normal cell to become cancerous. Defects in the RAS/RAF/MEK/ERK signaling pathway are closely associated with the development of human tumors, such as melanoma, colon, lung and thyroid cancers. This pathway has emerged as a significant focus for molecular targeted cancer therapy and MEK inhibitors have the potential for broad utility in the treatment of human cancers driven by activation of this pathway. In this work we used both MEK inhibition and oral bioavailability data for a series of isothiazole derivatives. Isothiazole derivatives are a very important group of biologically active compounds that have recently gained attention as potent MEK inhibitors. The aim of our study is the identification of novel series of potent MEK inhibitors with favorable ADME properties. We have developed validated QSAR models to quantitatively describe and predict the relationship between structural characteristics, activity and oral bioavailability. Applicability domain based on similarity measurements has been determined. A thorough discussion has been conducted to help researchers to design novel chemistry driven molecules with desired inhibition activity and bioavailability.