Alox12e Inhibitors

Chemical inhibitors of Alox12e include a variety of compounds that function by different mechanisms to inhibit the activity of this lipoxygenase enzyme. Nordihydroguaiaretic acid (NDGA) and its analog masoprocol directly target the active site of Alox12e, effectively blocking the enzyme's ability to interact with its polyunsaturated fatty acid substrates and thus inhibit its function. Similarly, baicalein and esculetin are known for their selective inhibition of lipoxygenase enzymes, including Alox12e. By specifically binding to the enzyme, they prevent the usual oxygenation of fatty acids that Alox12e catalyzes. Zileuton, although a selective 5-lipoxygenase inhibitor, can also attenuate Alox12e activity by reducing the substrate availability for the enzyme, namely arachidonic acid, thus indirectly decreasing the production of leukotrienes which are vital products of Alox12e's enzymatic reaction.

Caffeic acid inhibits Alox12e by a similar substrate deprivation strategy, blocking the formation of leukotrienes and hydroxyeicosatetraenoic acids (HETEs), which are downstream products of the Alox12e enzyme. The inhibition of 5-lipoxygenase-activating protein (FLAP) by MK-886 results in a decreased synthesis of leukotrienes, which indirectly influences Alox12e activity by altering its reaction cascade. Curcumin and quercetin, both potent lipoxygenase inhibitors, can inhibit Alox12e by preventing the enzyme from interacting with its fatty acid substrates. Green tea extract, and its component epigallocatechin gallate, inhibits Alox12e by directly binding to its active site and blocking the catalysis of its natural reactions. Acetaminophen, predominantly recognized as a COX inhibitor, also exhibits some degree of lipoxygenase inhibition and can inhibit Alox12e by reducing its ability to oxidize fatty acids, central to the enzyme's function. Each of these chemicals applies a distinct inhibitory effect on Alox12e, either by direct active site blockade or indirectly through the modulation of substrate availability and downstream product synthesis.