Serine/arginine-rich protein kinase 1 (SRPK1) targets proteins that contain multiple serine/arginine (SR) dipeptides, including SR-rich splicing factor 1, SRSF1. SRPIN340 is an isonicotinamide compound that inhibits SRPK1 (Ki = 0.89 μM). It is about 10-fold less effective against SRPK2 and does not inhibit the related SRPKs, Clk1 and Clk4. SRPIN340 suppresses the propagation of Sindbis virus in Vero cells and the replication of hepatitis C virus in Huh7/Rep-Feo-2a cells. By blocking SRPK1-mediated phosphorylation of SRSF1, SRPIN340 modulates alternative splicing of VEGF, reducing neovascularization both in cells and in animals.
