Structure-Based Drug Design of Novel MARK-3 Inhibitors in Cancer

MARK3 (microtubule affinity regulating kinase 3) is a serine/threonine protein kinase. The protein kinases have a regulatory role in cell biology, involved in a variety of cellular processes such as apoptosis, cell cycle, cytoskeletal rearrangement, immune response, nervous system function, and transcription. Deregulation of these protein kinases triggers a variety of diseases such as cancer, diabetes, cardiovascular and nervous system disorders, which highlights this family of proteins as druggable targets. However, the development of competitive inhibitors to protein kinases is a challenging task due to the high level of similarity between members of this family, ranging from 50 to 85 % of sequence identity. The structure-based techniques were performed to design novel MARK3 inhibitors. Structure-based virtual screening experiments were performed selecting 20 compounds whose activity profiles were predicted using PASS and DEREK softwares. In addition, the top docking solutions were evaluated by molecular dynamics simulations.