Differential gene expression analysis of RAGE-S100A6 complex for target selection and the design of novel inhibitors for anticancer drug discovery.

Abstract

Receptor for advanced glycation end products (RAGE), a member of the immunoglobulin family, interactions with its ligands trigger downstream signaling and induce an inflammatory response linked to diabetes, inflammation, carcinogenesis, cardiovascular disease, and a variety of other human disorders. The interaction of RAGE and S100A6 has been associated with a variety of malignancies. For the control of RAGE-related illnesses, there is a great demand for more specialized drug options. To identify the most effective target for combating human malignancies associated with RAGE-S100A6 complex, we conducted single and differential gene expression analysesof S100A6 and RAGE, comparing normal and malignant tissues. Further, a structure-based virtual screening was conducted using the ZINC15 database. The chosen compounds were then subjected to a molecular docking investigation on the RAGE active site region, recognized by the various cancer-related RAGE ligands. An optimized RAGE structure was screened against a library of drug-like molecules. The screening results suggested that three promising compounds were presented as the top acceptable drug-like molecules with a high binding affinity at the RAGE V-domain catalytic region. We depicted that these compounds may be potential RAGE inhibitors and could be used to produce a successful medication against human cancer and other RAGE-related diseases based on their various assorted parameters, binding energy, hydrogen bonding, ADMET characteristics, etc. MD simulation on a time scale of 50 ns was used to test the stability of the RAGE-inhibitor complexes. Therefore, targeting RAGE and its ligands using these drug-like molecules may be an effective therapeutic approach.