تصميم مثبطات محتملة للبروتين XIAP المضاد للموت الخلوي باستخدام النمذجة الجزيئية

Abstract

XIAP is a member of the Anti-apoptotic IAP family proteins. It plays essential roles related to different cell death pathways, in addition to its involvement in cancer diseases development; including breast and lung cancer. This work aims to discover potential inhibitors of the XIAP protein using molecular modeling study. A new library of chemical compounds was designed based upon the structure of previous inhibitors; docking study of these compounds was effectuated within the BIR3 domain of XIAP protein. Binding affinity and mode of fixation of these compounds were determined within the prepared active pocket of the protein.

The study led to the discovery of 11 compounds with high binding affinity; these molecules consist of two rings separated by an eight-atom linker. We have completed the research by Drug-Likeness Properties study according to Lipinski and Weber's rules, the study led to discover five top hits for further later studies.