Dabrafenib, as a Novel Insight into Drug Repositioning Against Secretory Group IIa Phospholipase A2

作者：Jung Byeongjin; Kim Jaehong; Bae Jong Sup

来源：International Journal of Pharmacology, 2016, 12(4): 415-421.

DOI：10.3923/ijp.2016.415.421

• Dabrafenib
• HUVECs
• sPLA2-IIa
• inflammation
• mice
• drug repositioning

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 IIa phospholipase A2 (sPLA2-IIa) is enhanced by development of inflammatory disorders. In this study, sPLA2-IIa 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 of sPLA2-IIa 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-IIa 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-IIa expression and activity in response to the inflammatory diseases.

• 出版日期2016