In Silico Screening of Multi-Domain Targeted Inhibitors for PTK6: A Strategy Integrating Drug Repurposing and Consensus Docking

Ms. T. Chaitanya Kumari, 2Mr. Ch. Kishore,3Mrs. M. Sandhya Rani

» doi: http://https://ijpsl.co.in//.2023.v13.i04.pp01-11

Abstract

Protein tyrosine kinase 6, or BRK, is an intracellular tyrosine kinase that does not bind to receptors and is a member of the Src kinases family. Similar to other Src kinases, PTK6 has three domains: SH3, SH2, and SH1, which are responsible for tyrosine kinase activity. Despite extensive research into developing PTK6 inhibitors that specifically target the SH1 domain—the part of the protein that is involved in kinase activity across several pathways—it has been shown that this region alone is insufficient to limit PTK6 activity. Research that followed established that PTK6's SH2 and SH3 domains play an essential role in substrate binding and intramolecular interactions. As a result, it is critical to find PTK6 inhibitors that target both the SH1 and SH2 and SH3 domains. Our in silico structural-based virtual screening method, which includes drug repurposing and a consensus docking technique, has yielded four ligand candidates that can inhibit PT6K's tyrosine kinase domain and SH2/SH3 domains at the same time. This discovery raises the possibility of new avenues for therapeutic therapies involving the suppression of PTK6.