Abstract
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.
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Acknowledgements
DT is thankful to University Grants Commission, New Delhi for financial support in the form of UGC—BSR (RFSMS) Senior Research Fellowship. Y.S. is thankful to Human Resource Development for Health Research, New Delhi (F.No.V.25011/542-HRD/2016-HR). We are very grateful to the Journal Editor, anonymous reviewers, and Prof. P. Sreedhara Reddy, Department of Physics, Sri Venkateswara University, Tirupati for their constructive and useful comments which improve the scientific content of the original paper.
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Daggupati, T., Chitrala, K., Pamanji, R. et al. Molecular screening and analysis of novel therapeutic inhibitors against c-Jun N-terminal kinase. Med Chem Res 26, 2112–2118 (2017). https://doi.org/10.1007/s00044-017-1919-5
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DOI: https://doi.org/10.1007/s00044-017-1919-5