bromoenol lactone

Bromoenol lactone ((6E)-Bromoenol lactone) is a selective calcium-dependent phospholipase A2 (iPLA2β) and serine protease inhibitor that attenuates nicotine-induced breast cancer cell proliferation and migration, inhibits voltage-gated Ca2+ and transient receptor potential classical channels, and inhibits carrageenan-induced prostaglandin production and hyperalgesia in rat hind paws.

The phospholipases are an extensive family of lipid hydrolases that function in cell signaling, digestion, membrane remodeling, and as venom components. The calcium-independent phospholipases (iPLA2) are a PLA2 subfamily closely associated with the release of arachidonic acid in response to physiologic stimuli. (R)-Bromoenol lactone ((R)-BEL) is an irreversible, chiral, mechanism-based inhibitor of calcium-independent phospholipase γ (iPLA2γ). Unlike (S)-BEL, (R)-BEL does not inhibit iPLA2β except at high doses of 20-30 μM. (R)-BEL inhibits human recombinant iPLA2γ with an IC50 of approximately 0.6 μM.

(S)-Bromoenol lactone ((S)-BEL) is a mechanism-based, irreversible inhibitor of calcium-independent phospholipase A2 (iPLA2). In contrast to its enantiomer (R)-BEL, (S)-BEL exhibits a preference for iPLA2γ (Group VIB), typically being about 10- to 100-fold more potent at inhibiting iPLA2γ than iPLA2β (Group VIA). This compound, used in conjunction with (R)-BEL, is a critical pharmacological tool for discriminating the specific functions of iPLA2β versus iPLA2γ in processes such as cellular signaling, arachidonic acid release, and smooth muscle contraction.