Chemical Information

Biological Activity of SRPIN340

Description:
IC50 Value: 0.89 uM (SRPK1) [1]
 SRPIN340 is a serine/arginine-rich protein kinase (SRPK)-specific inhibitor with an IC50 value of 0.89 uM (SRPK1).
in vitro: SRPIN340 potently inhibits SRPK1 kinase activity, with a Kivalue of 0.89 μM. SRPIN340 inhibits SR phosphorylation by SRPK in Flp-In293 cells and promotes degradation of SRp75 in a dose-dependent manner (Fig. 4). Thus, because retention of SRp75 is necessary for HIV expression, SRPIN340 emerges as a potential inhibitor of HIV production. SRPIN340 (40 μM) rescues Vero cells from the cytopathic effect of Sindbis virus. The SRPIN340 IC50 for Sindbis virus propagation was 60 μM [1]. SRPIN340, suppressed in a dose-dependent fashion expression of a hepatitis C virus (HCV) subgenomic replicon and replication of the HCV-JFH1 clone in vitro. The inhibitory effects were not associated with antiproliferative or nonspecific cytotoxic effects on the host cells. Overexpression of SRPK1 or SRPK2 resulted in augmentation of HCV replication, while small interfering RNA (siRNA) knockdown of the SRPKs suppressed HCV replication significantly [2]. SRPIN340 inhibited CNV formation in a dose-dependent manner. Compared with the vehicle, SRPIN340 significantly decreased the protein levels of VEGF, MCP-1, ICAM-1, and consequently inhibited macrophage infiltration. Furthermore, SRPIN340 suppressed the gene expression levels of total Vegf and exon 8a-containing Vegf isoforms [3].
in vivo: No adverse effects were observed when SRPIN340 was orally administrated to rats, even at the highest SRPIN340 dose (2,000 mg/kg). In addition, no abnormalities in chromosomal structure and chromosome number were observed when SRPIN340 was administrated to CHO cells in the culture medium at the highest SRPIN340 dose (5 mg/ml) for 24 h [1].
Toxicity: The rudimentary toxicity data available for SRPIN340 is promising with respect to the potential for use of this compound as a therapeutic. No adverse effects were observed when SRPIN340 was orally administrated to rats, even at the highest SRPIN340 dose (2,000 mg/kg). In addition, no abnormalities in chromosomal structure and chromosome number were observed when SRPIN340 was administrated to CHO cells in the culture medium at the highest SRPIN340 dose (5 mg/ml) for 24 h [1].
Clinical trial:
 

References on SRPIN340

[1]. Fukuhara T, et al. Utilization of host SR protein kinases and RNA-splicing machinery during viral replication. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11329-33.
[2]. Karakama Y, et al. Inhibition of hepatitis C virus replication by a specific inhibitor of serine-arginine-rich protein kinase. Antimicrob Agents Chemother. 2010 Aug;54(8):3179-86.
[3]. Dong Z, et al. Specific inhibition of serine/arginine-rich protein kinase attenuates choroidal neovascularization. Mol Vis. 2013;19:536-43.