Targeting Serine-Arginine Protein Kinase 1 (SRPK1): Roles in Cellular Processes and Regulation through Selective Inhibitors

Soha Aggarwal

Abstract: Protein kinases are a family of attractive enzyme targets for drug design, with significant relevance to various diseases, including cancer. Serine-arginine protein kinase 1 (SRPK1) is specifically responsible for the phosphorylation of serine/arginine (SR)-rich proteins, such as Alternative Splicing Factor/Splicing Factor 2 (ASF/SF2), which is involved in mRNA processing. Overexpression of ASF/SF2 has been observed in various diseases and plays a crucial role in promoting cell survival. The phosphorylation of SR proteins by SRPK1 is a significant regulatory mechanism in cancer progression. In the search for potential anticancer agents to inhibit SRPK1 activity, we utilized in-silico methods to screen natural and drug-like compound databases for specific inhibitors of SRPK1. Five promising inhibitors were identified, with SRPKIN-1 emerging as the most potent. Structural analysis of the SRPK1-SRPKIN-1 complex revealed that SRPKIN-1 uniquely binds to the ATP-binding site, potentially blocking SRPK1 activity and disrupting its recruitment. These findings suggest that SRPKIN-1 could serve as a lead compound paving the way for the development of potent and specific inhibitors of SRPK1 for designing of novel potential anticancer inhibitor is inferred from the current studies.

Keywords: Serine arginine protein kinase 1 (SRPK1), Splicing, Phosphorylation, Protein kinase, Structural analysis