Cell lines

A375, Omm2.5, Mel270 and 92.1 cells

Preparation method

The solubility of this compound in DMSO is >10.9mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

10 μM; 24 hours

Applications

In A375 cells, SRPIN340 resulted in a 54% reduction in the IGF-1 induced nuclear localisation of SRSF1. In Mel270 cells, SRPIN340 significantly reduced the proportion of nuclear SRSF1 compared with IGF-1 treatment alone. In A375, Omm2.5 and 92.1 cells, SRPIN340 reduced total VEGF protein.

Animal models

Mice bearing A375-untransfected tumours

Dosage form

100 μl of 20 μg/ml SRPIN340 (diluted 100× in PBS from 2mg/ml stock in DMSO); injected daily into the peritumoral space

Application

In mice bearing A375-untransfected tumours, SRPIN340 significantly reduced tumour growth compared with DMSO control-injected tumours. SRPIN340 also reduced total VEGF expression and significantly reduced microvascular density (MVD).

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

SRPIN340 is a highly selective inhibitor of SR protein phosphorylation with a Ki value of 0.89μM for SRPK1 [1].

SRPIN340 has been revealed to inhibit replication of HIV-1 and other viruses that require SR protein-dependent RNA processing for the propagation in HIV-1 transfected or infected Flp-In293 cell lines. In addition, SRPIN340 has been reported to significantly inhibit SRPK1 and SRPK2 kinase activity but not potently inhibit other SRPKs, such as Clk1 and Clk4 with a Ki value of 0.89μM for SRPK1. Besides, SRPIN340 has been exhibited to dose-dependently promote degradation of SRp75 which is necessary for HIV expression. Moreover, SRPIN340 has shown the inhibition of propagation of Sindbis virus with an IC50 of 60μM and the protection against the cytopathic effect of Sindbis virus [1].

References:
[1] Fukuhara T1, Hosoya T, Shimizu S, Sumi K, Oshiro T, Yoshinaka Y, Suzuki M, Yamamoto N, Herzenberg LA, Herzenberg LA, Hagiwara M.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. Epub 2006 Jul 13.