Identifying bioactive phytoconstituents as C terminal Src kinase inhibitors: a virtual screening and molecular simulation approach

Tyrosine-protein kinase CSK otherwise known as C-terminal Src kinase (CSK), is involved in multiple
pathways and processes, including regulating cell growth, differentiation, migration, and immune
responses. Altered expression of CSK has been associated with various complexities, including cancer,
CD45 deficiency, Osteopetrosis and lupus erythematosus. Important auxiliary roles of CSK in cancer
progression make it a crucial target in developing novel anticancer therapy. Thus, CSK inhibitors are of
concern as potent immuno-oncology agents. In this perspective, phytochemicals can be a significant
source for unraveling novel CSK inhibitors. In this study, we carried out a systematic structure-based
virtual screening of bioactive phytoconstituents against CSK to identify its potential inhibitors. After a
multi-step screening process, two hits (Shinpterocarpin and Justicidin B) were selected based on their
druglike properties and binding affinity towards CSK. The selected hits were further analyzed for their
stability and interaction via all-atom molecular dynamics (MD) simulations. The selected hits indicated
their potential as selective binding partners of CSK, which can further be used for therapeutic development against CSK-associated malignancies.