Arachidonate 12-lipoxygenase (ALOX12) (ALOX12)

Arachidonate 12-lipoxygenase (ALOX12) is a non-heme iron-containing enzyme that plays a pivotal role in the metabolism of polyunsaturated fatty acids, specifically converting arachidonic acid into 12(S)-hydroperoxyeicosatetraenoic acid (12(S)-HPETE) [1, 2]. This metabolite is rapidly reduced to 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), a potent bioactive lipid involved in various physiological and pathological processes [2, 3]. Primarily expressed in platelets, ALOX12 is a key regulator of platelet reactivity and thrombus formation, making it a target of interest for anti-platelet therapy in cardiovascular diseases [4, 5]. Additionally, ALOX12 has been implicated in the pathogenesis of type 2 diabetes by promoting pancreatic beta-cell inflammation and apoptosis, as well as in cancer progression where it facilitates tumor cell survival and metastasis [6, 7]. Therapeutic strategies focusing on ALOX12 involve the development of small-molecule inhibitors, such as ML355, which aim to reduce 12(S)-HETE production to mitigate inflammatory and thrombotic risks [4, 8]. Achieving high selectivity for ALOX12 over other lipoxygenase isoforms remains a primary focus for drug development to avoid off-target effects [8, 9].

Other names

12-LOXPlatelet-type 12-lipoxygenase12S-lipoxygenaseLOG12Arachidonate 12-lipoxygenase, 12S-type

Inhibition of the enzyme's catalytic activity to prevent the oxygenation of arachidonic acid, thereby reducing the production of pro-inflammatory and pro-thrombotic 12(S)-HETE [2, 4].