Abstract
Aim: SMYD3 enzyme is overexpressed in many types of cancer and its role in the methylation of cytoplasmic mitogen-activated protein kinase, kinase kinase 2 (MAP3K2), has been linked to promotion of Kras-driven cancer in pancreatic ductal and lung adenocarcinoma. Materials & methods: A hybrid 3D structure-based pharmacophore model was generated using crystal structures of SMYD3 complexed with sinefungin and was used to search for potential SMYD3 inhibitors through virtual screening of the Maybridge database. The retrieved hits from screening were further docked into the binding site of SMYD3 using CDOCKER docking algorithms. The top-ranked hits were selected and their inhibitory activity was evaluated. Results & conclusion: The results obtained helped us to find an SMYD3 small molecule hit inhibitor scaffold.
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Supplementary data
To view the supplementary data that accompany this paper please visit the journal website at:www.tandfonline.com/doi/full/10.2217/epi-2016-0184
Financial & competing interests disclosure
The authors wish to thank the Deanship of Scientific Research at Jordan University of Science and Technology for financial support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.