The 85 kD cytosolic phospholipase A2α (cPLA2α) selectively hydrolyzes arachidonic acid from the sn-2 position of membrane phospholipids, generating substrate for eicosanoids and platelet-activating factor.1 RSC-3388 is a pyrrolidine derivative that acts as a potent inhibitor of cPLA2α, suppressing both recombinant human cPLA2 in vitro (IC50 = 1.8 nM) and cellular PLA2 activity in cells stimulated with the calcium ionophore A23187 (IC50 = 22 nM). In the human acute monocytic leukemia cell line THP-1, RSC-3388 blocks the production of prostaglandin E2 (IC50 = 31 nM) and leukotriene C4 (IC50 = 13 nM).2 RSC-3388 also reduces skin inflammation in murine models of atopic dermatitis, presumably through its inhibitory effects on cPLA2.3
1.Niknami, M., Patel, M., Witting, P.K., et al.Molecules in focus: Cytosolic phospholipase A2-αInt. J. Biochem. Cell Biol.41994-997(2009)
2.Seno, K., Okuno, T., Nishi, K., et al.Pyrrolidine inhibitors of human cytosolic phospholipase A2J. Med. Chem.43(6)1041-1044(2000)
3.Yamamoto, M., Haruna, T., Imura, K., et al.Inhibitory effect of a potent and selective cytosolic phospholipase A2α inhibitor RSC-3388 on skin inflammation in micePharmacology81301-311(2008)
