Dabrafenib, as a novel insight into drug repositioning against secretory group IIa phospholipase A2

The screening of bioactive compound libraries can be an effective approach for repositioning FDA-approved drugs or discovering new treatments for human diseases. The expression of secretory group lla phospholipase A2 (sPLA2-lla) is enhanced by development of inflammatory disorders. In this study, sPLA2-lla expression was induced in the lipopolysaccharide(LPS)-stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and mice to evaluate the effect of dabrafenib. This study illustrates drug repositioning with dabrafenib (DAB) for the modulation ofsPLA2-lla expression and activity. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Results showed that dabrafenib remarkably suppressed the LPS-mediated protein expression and activity of sPLA2-lla via inhibition of phosphorylation of cytosolic phospholipase A2 (cPLA2)and extracellular signal-regulated kinase (ERK) 1/2. These results demonstrated that dabrafenib might play an important role in the modulation of sPLA2-lla expression and activity in response to the inflammatory diseases.