c-rel transkripsiyon faktörüne karşılık yapıya dayandırılmış ilaç dizaynı

NF-?B signaling cascade plays a major role in many physiological processes such as immune and inflammatory responses, developmental processes, cellular growth, and apoptosis. The dysregulation of NF-?B pathway and other signaling pathways that control its activity is a common feature of many diseases including cancer development and progression, cardiovascular and inflammatory diseases. c-Rel is one of the member of NF-?B transcription factor family. It is shown that c-Rel proto-oncogene is the only NF-?B family member that can malignantly transform cells in culture. There have been various ongoing studies focused on blocking NF-?B signaling by preventing binding of transcription factor to its target sites on DNA. In this study, we rather focus on termination of NF-?B signaling. We propose a novel way of inhibiting NF- ?B action by removing it from DNA. c-Rel is chosen for this study because it is the most specialized member of NF-?B family and termination of c-Rel response will have the least undesired side effects. We first predict the structure of human c-Rel protein with a template based homology modeling server. The critical residues that will induce unbinding of c-Rel from DNA are determined by Gaussian Network Model. These residues are considered as drug interaction site and virtual screening studies is performed against c-Rel. Molecular modifications are applied to best hit compounds to increase the binding affinities. Potential drug molecules are then docked to other NF-?B members to check specificity to c-Rel.