BEC (hydrochloride)

BEC hydrochloride is a slow-binding and competitive Arginase II inhibitor with K_i of 0.31 μM and 30 nM at pH 7.5 and pH 9.5, respectively^[1]. IC50 & Target: Ki: 0.31 μM (BEC hydrochloride, at pH 7.5) and 30 nM (BEC hydrochloride, at pH 9.5)^[1] In Vitro: The X-ray crystal structure of the arginase-BEC complex has been determined at 2.3 ? resolution from crystals perfectly twinned by hemihedry. The structure of the complex reveals that the boronic acid moiety undergoes nucleophilic attack by metal-bridging hydroxide ion to yield a tetrahedral boronate anion that bridges the binuclear manganese cluster, thereby mimicking the tetrahedral intermediate (and its flanking transition states) in the arginine hydrolysis reaction^[2]. In Vivo: Administration of the arginase inhibitor BEC decreases arginase activity and causes alterations in NO homeostasis, which are reflected by increases in S-nitrosylated and nitrated proteins in the lungs from inflamed mice. BEC enhances perivascular and peribronchiolar lung inflammation, mucus metaplasia, NF-κB DNA binding, and mRNA expression of the NF-κB-driven chemokine genes CCL20 and KC, and leads to further increases in airways hyperresponsiveness^[3].