Gemilukast is an orally active and potent dual cysteinyl leukotriene 1 and 2 receptors (CysLT1 and CysLT2) antagonist, with IC50s of 1.7, 25 nM for human CysLT1 and CysLT2, respectively.
Gemilukast is an orally active and potent dual cysteinyl leukotriene 1 and 2 receptors (CysLT1 and CysLT2) antagonist, with IC50s of 1.7, 25 nM for human CysLT1 and CysLT2, respectively[1]. Both Gemilukast (ONO-6950) and montelukast inhibit human CysLT1 receptor-mediated calcium response with IC50 values of 1.7 and 0.46 nM, respectively[2].
Gemilukast at 0.03 to 10 mg/kg, p.o. dose-dependently attenuates LTC4-induced bronchoconstriction with almost complete inhibition at 3 mg/kg. The inhibitory effect of Gemilukast on LTC4-induced bronchoconstriction is significantly stronger than that of montelukast at the dose of 1 mg/kg or more. Gemilukast (0.03 to 1 mg/kg, p.o.) dose-dependently attenuates LTD4-induced airway vascular hyperpermeability with complete inhibition at 0.3 mg/kg. Gemilukast at 0.1 to 3 mg/kg, p.o. dose-dependently inhibits OVA-induced bronchoconstriction. The inhibitory effect of Gemilukast at 3 mg/kg is significantly greater than that of montelukast alone and comparable to that of combination therapy with montelukast and BayCysLT2RA[2].
[1]. Itadani S, et al. Discovery of Gemilukast (ONO-6950), a Dual CysLT1 and CysLT2 Antagonist As a Therapeutic Agent for Asthma. J Med Chem. 2015 Aug 13;58(15):6093-113. [2]. Yonetomi Y, et al. Effects of ONO-6950, a novel dual cysteinyl leukotriene 1 and 2 receptors antagonist, in a guinea pig model of asthma. Eur J Pharmacol. 2015 Oct 15;765:242-8.