TMEM16A activator E(act) (Eact) is a small molecule activator of calcium-activated chloride channel TMEM16A (ANO1) with EC50 of 3 uM. E(act) is effective in producing Cl− current in mouse TMEM16A. E(act) shows activation by Eact of TMEM16B, the other TMEM16 isoform having CaCC activity, does not affect CFTR Cl− conductance or ENaC Na+ conductance. E(act) inhibits TMEM16A Cl− conductance, providing further evidence for direct TMEM16A binding. E(act) increases CaCC conductance in human salivary and airway submucosal gland epithelial cells, and IL-4 treated bronchial cells, and stimulates submucosal gland secretion in human bronchi and smooth muscle contraction in mouse intestine.
