Molecular screening and analysis of novel therapeutic inhibitors against c-Jun N-terminal kinase

c-Jun N-terminal kinase is an important regulator, activating several transcription factors in response to proinflammatory cytokines, ultraviolet radiations, environmental stress, hypoxia and osmotic shock and is known to be reported a cause for many diseases, such as diabetes, cancer, inflammation, stroke, etc. In the present study, we aim to predict novel therapeutic leads against c-Jun N-terminal kinase-3 by employing structure based virtual screening in combination with various in silico toxicity filters. We screened ZINC database virtually using a known potent c-Jun N-terminal kinase inhibitor, SP600125, as reference molecule. We obtained 128 molecules sharing ≥70% structure identity with SP600125. These 128 compounds were subjected to virtual screening and various toxicity filters. Finally, three molecules were identified as novel c-Jun N-terminal kinase inhibitors. Further binding mode analysis suggested that these molecules inhibit c-Jun N-terminal kinase activity through binding the adenosine triphosphate binding pocket.