cPLA2α is an intracellular calcium dependent PLA2. It is expressed in a wide variety of tissues and cells. Firstly, cPLA2α can catalyze the release of arachidonic acid (AA) from phospholipids in the cell membrane. And it results the formation of PGE2, PGD2, PGF2α, PGI2, or TXA2 by tissue specific isomerases. Secondly, PLA2α and cyclooxygenase-2 (COX-2) have a high expression at the site of inflammation. Furthermore, based on its role in the production of prostaglandins (PGs), blocking cPLA2α is effective at inhibiting inflammatory pain. Today, we will introduce a cPLA^2α inhibitor — Efipladib.

Efipladib is a potent, selective and orally active cPLA^2α inhibitor for inflammation research

In vitro, Efipladib is a cPLA^2α inhibitor with an IC₅₀ of 0.04 μM and a K_d of 0.067 μM. Then Efipladib (10-25 μM; 24-72 h) can increase COX-1 and PGE2 levels in PC3 and LNCaP cells.

In vivo, Firstly, Efipladib (100 mg/kg; p.o.; BID for 31 days) can reverse the severity in the mouse collagen-induced arthritis (CIA) model. Secondly, Efipladib (100 mg/kg; p.o.; once) significantly inhibits the nociceptive response 1 h after administration in the rat Complete Freund’s Adjuvant (CFA) nociception model. Thirdly, Efipladib is unable to cross the BBB to gain access to the central compartment. In addition, Efipladib (100 nM; i.t.; 5 μL) reduces PGE2 levels in the cerebrospinal fluid in rats.

In a word, Efipladib is an orally active cPLA^2α inhibitor and can be used for the research of inflammation.

Reference:

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[4] Niknami M, et al. Biochim Biophys Acta. 2010 Jul;1801(7):731-7.