Identification of gefitinib off-targets using a structure-based systems biology approach; their validation with reverse docking and retrospective data mining

• DOI: 10.1038/srep33949
• Publication Date: 2016-09-22T09:42:42Z
• Authors: Nidhi Verma; Amit Kumar Rai; Vibha Kaushik; Daniela Brünnert; Kirti Raj Chahar; Janmejay Pandey; Pankaj Goyal
• Keywords: Druggability; Docking (animal)

Abstract Gefitinib, an EGFR tyrosine kinase inhibitor, is used as FDA approved drug in breast cancer and non-small cell lung treatment. However, this has certain side effects complications for which the underlying molecular mechanisms are not well understood. By systems biology based silico analysis, we identified off-targets of gefitinib that might explain drugs. The crystal structure EGFR-gefitinib complex was binding pocket similarity searches on a druggable proteome database (Sc-PDB) by using IsoMIF Finder. top 128 hits putative were validated reverse docking approach. results showed have efficient with gefitinib. human specific confirmed further analyzed their links biological process clinical disease pathways retrospective studies literature mining, respectively. Noticeably, many study reported previous high-throughput screenings. Interestingly, present reveals may positive reducing brain bone metastasis, be useful defining novel treatment regime. We propose system wide approach could during new development to minimize effect prospective drug.