In Silico Screening of Multi-Domain Targeted Inhibitors for PTK6: A Method Combining Consensus Docking and Drug Repurposing
Keywords:
PTK6, drug repurposing, consensusdocking, structure based virtual screening, in silico studiesAbstract
As a non-receptor intracellular tyrosine kinase belonging to the Src kinase family, protein tyrosine kinase 6 (PTK6) is often
referred to as breast tumour kinase (BRK).PTK6 has structural similarities with other Src kinases, including a tyrosine kinase domain
(SH1), a Src homology 2 (SH2) domain, and a Src homology 3 (SH3) domain.Although a lot of work has gone into creating PTK6
inhibitors that target the SH1 domain, which is in charge of kinase activity in a number of pathways, it has been shown that PTK6
activity cannot be successfully suppressed by only blocking the SH1 domain. The role of SH2 and SH3 domains in intramolecular and
substrate binding interactions, which are essential for PTK6 activity, has been shown by further experiments. Therefore, it becomes
essential to identify PTK6 inhibitors that target the SH2 and SH3 domains in addition to the SH1 domain. Four putative ligands that
may concurrently inhibit the tyrosine kinase domain and SH2/SH3 domains of PT6K have been effectively discovered by an
insilicostructural-based virtualscreening technique that incorporates drugre purposing and a consensus docking approach. This
discovery raises the possibility of treatment approaches including PTK6 inhibition
