Abediterol has higher β2-receptor affinity and in vitro bronchodilatory potency than other long-acting β2-agonists, with good selectivity

Introduction Abediterol (LAS100977) is a novel, long-acting, inhaled s2-receptor agonist in Phase II development for asthma and COPD. We report the in vitro potency, selectivity and duration of action (DoA) of abediterol vs indacaterol, olodaterol and vilanterol. Methods Affinity studies used chinese hamster ovary cells expressing human, guinea pig (GP) or dog β1 or β2 receptors. Potency, onset and DoA were assessed in vitro in GP trachea. Onset (time to 50% maximal relaxation) and DoA (time to 50% recovery of maximal contraction) were assessed at IC80 concentration. β1-receptor activity was assessed in GP left heart atria at cumulative concentrations (1 nM–10 μM). Results Abediterol had the highest s2-receptor affinity vs comparators; all compounds had substantially lower s1-receptor affinity (Table). The potency of abediterol (0.1 nM) was 5-, 77- and 80-fold greater than olodaterol, indacaterol and vilanterol, respectively. Abediterol had slightly slower onset vs comparators. DoA of abediterol was similar to vilanterol (both >480 min) and longer than indacaterol (218 min) and olodaterol (325 min). Abediterol, olodaterol and vilanterol all had very low potency in atrial tissue (EC50 >10 μM), vs 6.3 μM for indacaterol. Conclusion Abediterol is a potent s2-receptor agonist with a long DoA in tracheal tissue and low activity in atrial tissue, suggesting that abediterol may offer reduced potential for cardiac effects in humans. View this table: Receptor affinity IC50 (nM)