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The Ca
2+
activated Cl
−
channels (CaCCs) play a multitude of important physiological functions. A number of candidate proteins have been proposed to form CaCC, but only two families, the bestrophins and the TMEM16 proteins, recapitulate the properties of native CaCC in expression systems. Studies of endogenous CaCCs are hindered by the lack of specific pharmacology as most Cl
−
channel modulators lack selectivity and a systematic comparison of the effects of these modulators on TMEM16A and bestrophin is missing. In the present study, we studied seven Cl
−
channel inhibitors: niflumic acid (NFA), NPPB, flufenamic acid (FFA), DIDS, tannic acid, CaCC
inh
-A01 and T16A
inh
-A01 for their effects on TMEM16A and bestrophin-1 (Best1) stably expressed in CHO (Chinese hamster ovary) cells using patch clamp technique. Among seven inhibitors studied, NFA showed highest selectivity for TMEM16A (IC
50
of 7.40 ± 0.95 μM) over Best1 (IC
50
of 102.19 ± 15.05 μM). In contrast, DIDS displayed a reverse selectivity inhibiting Best1 with IC
50
of 3.93 ± 0.73 μM and TMEM16A with IC
50
of 548.86 ± 25.57 μM. CaCC
inh
-A01 was the most efficacious blocker for both TMEM16A and Best1 channels. T16A
inh
-A01 partially inhibited TMEM16A currents but had no effect on Best1 currents. Tannic acid, NPPB and FFA had variable intermediate effects. Potentiation of channel activity by some of these modulators and the effects on TMEM16A deactivation kinetics were also described. Characterization of Cl
−
channel modulators for their effects on TMEM16A and Best1 will facilitate future studies of native CaCCs.