Description
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 (K
i = 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.
References
1) Fukuhara?et al.?(2006),?Utilization of host SR protein kinases and RNA-splicing machinery during viral replication; Proc. Natl. Acad. Sci. USA,?103?11329
2) Gammons?et al.?(2013),?SRPK1 inhibition modulates VEGF splicing to reduce pathological neovascularization in a rat model of retinopathy of prematurity; Invest. Ophthalmol. Vis. Sci.,?54?5797
3) Gammons?et al.?(2014),?Targeting SRPK1 to control VEGF-mediated tumour angiogenesis in metastatic melanoma; Br. J. Cancer,?111?477
