Differential gene expression analysis of RAGE‐S100A6 complex for target selection and the design of novel inhibitors for anticancer drug discovery. Issue 2 (11th December 2022)

• Record Type: Journal Article
• Authors: Faruqui, Tabrez; Singh, Garima; Khan, Salman; Khan, Mohd Sajid; Akhter, Yusuf
• Is Part Of: Journal of cellular biochemistry. Volume 124:Issue 2(2023)
• Page Start: 205
• Page End: 220
• Publication Date: 2022-12-11
• Subjects: gene expression -- molecular docking -- molecular dynamics simulations -- receptor for advanced glycation end products -- S100A6 -- virtual screening; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.30356
• Languages: English
• ISSNs: 0730-2312

Abstract

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 analyses of 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.