Ki: 130 μM
EA4 is a rPLA2 inhibitor.
rPLA2, a calcium-dependent cytosolic phospholipase A2 (cPLA2), was initially isolated and characterized from bovine and human red blood cells. With a molecular mass of 42 kDa, cPLA2 shows biochemical properties similar to cPLA2 Type IV.
In vitro: It was found that EA4 was able to inhibit a Ca(2+) ionophore-induced arachidonic acid release from both human and bovine red blood cells, demonstrating that this enzyme was responsible for the Ca(2+)-dependent arachidonic acid release from mammalian red blood cells [1]. Another study found that in mouse hepatoma Hepa-1c1c7 cells, EA4 could cause a significant induction of the CYP1A1-mediated ethoxyresorufin O-deethylase activity time- and concentration-dependently, and such induction was accompanied by an increase of the Cyp1a1 mRNA transcription. Morevoer, in human cells including MCF-7 (human breast adenocarcinoma cell line), HepG2 (human hepatocarcinoma), and HL-60 (human promyelocytic cell line), the expression of CYP1A1 mRNA could be also induced by EA4 treatment. In addition, CYP1B1 mRNA was increased by EA4 in MCF-7 cells [2].
In vivo: Up to now, there is no animal in vivo data reported.
Clinical trial: So far, no clinical study has been conducted.
References:
1. Shin, H.S.,Chin, M.R.,Kim, J.S., et al. Purification and characterization of a cytosolic, 42-kDa and Ca2+-dependent phospholipase A2 from bovine red blood cells. The Journal of Biological Chemisty 277, 21086-21094 (2002).
2. Chun, Y.J.,Lee, B.Y.,Yang, S.A., et al. Induction of cytochrome P450 1A1 gene expression by a vitamin K3 analog in mouse hepatoma Hepa-1c1c7 cells. Molecules and Cells 12, 190-196 (2001).