SPHINX31

SPHINX31 (CAS No.: 1818389-84-2) is a potent and selective small-molecule inhibitor of serine/arginine-rich protein kinase 1 (SRPK1), a key regulator of alternative pre-mRNA splicing, widely used in studies of RNA processing and angiogenesis-related signaling. By inhibiting SRPK1 activity with nanomolar potency, SPHINX31 suppresses phosphorylation of the downstream substrate serine/arginine-rich splicing factor 1 (SRSF1), thereby modulating SRSF1-dependent splice site selection. This mechanism leads to a shift in vascular endothelial growth factor A (VEGF-A) splicing, reducing the expression of pro-angiogenic VEGF-A165a while promoting anti-angiogenic isoforms such as VEGF-A165b, ultimately attenuating angiogenic signaling pathways. In cellular systems, including cancer and retinal pigment epithelial cells, SPHINX31 demonstrates activity from nanomolar to low micromolar ranges, and in vivo studies have shown its ability to inhibit pathological neovascularization and associated inflammatory responses such as macrophage infiltration in ocular disease models. As a selective kinase inhibitor with demonstrated pathway specificity, SPHINX31 serves as a valuable chemical probe for investigating SRPK1-mediated splicing regulation and is broadly applied in studies of neovascular eye diseases, angiogenesis, and RNA splicing-targeted therapeutic strategies, with experimental concentrations or dosing regimens tailored to specific model systems and research objectives.