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Description: SPHINX31 is a novel, highly potent, selective, and cell bioactive inhibitor of the serine/arginine-rich protein kinase 1 (SRPK1) with IC50 value of 6 nM. It is selective for SRPK1 over a panel of 50 kinases at a concentration of 1 uM. Treatment with SPHINX31 inhibited SRPK1 activity and phosphorylation of serine/arginine splicing factor 1 (SRSF1), resulting in alternative splicing of VEGF-A from pro-angiogenic to antiangiogenic isoforms. SPHINX31 inhibits phosphorylation of serine/arginine-rich splicing factor 1 (SRSF1), an SRPK1 substrate, in PC3 cells (EC50 = 360 nM) and increases expression of the anti-angiogenic VEGF-A165b splice variant in retinal pigment epithelial (RPE) cells. In vivo, SPHINX31 (2 ug per eye) inhibits blood vessel growth and macrophage infiltration in the eyes of a mouse model of choroidal neovascularization. Serine/arginine-protein kinase 1 (SRPK1) regulates alternative splicing of VEGF-A to pro-angiogenic isoforms and SRPK1 inhibition can restore the balance of pro/antiangiogenic isoforms to normal physiological levels
References: ACS Chem Biol. 2017 Mar 17; 12(3):825-832.
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