AA-861

AA-861 (also known as Docebenone) is a potent and selective small-molecule inhibitor of **arachidonate 5-lipoxygenase (5-LO)**, a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes. Chemically a benzoquinone derivative, AA-861 was originally developed by **Takeda Pharmaceutical** and has been extensively used as a pharmacological tool in research to investigate leukotriene-mediated pathways in inflammation, asthma, and oncology. The drug acts as a direct covalent inhibitor, targeting specific cysteine residues (C416 and C418) to suppress enzyme activity. Beyond its primary 5-LO inhibition, AA-861 exhibits several off-target effects, including the inhibition of the prostaglandin E2 (PGE2) transporter **MRP4** (ABCC4), the inhibition of **TRPM7** channels, and the stimulation of **NADPH oxidase 4 (Nox4)** activity. While it was evaluated in clinical trials for conditions such as bronchial asthma and psoriasis in the late 1980s, its clinical development was discontinued, and it remains primarily a laboratory reagent.

Other names

Docebenone2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone