Figure 3.
Structure-activity analysis and synthesis of TMEM16A activators. A) Structural similarities between TMEM16A inhibitors and activators (common scaffolds shown in red). Apical membrane current measurements show activation of TMEM16A by Bact (top panels), inhibition of ionomycin (1 μM)-induced TMEM16A currents by pretreatment B and E class analogs (each 10 μM; bottom panels). B) Summary of structural determinants for TMEM16A activation. Left panel: Eact class. Right panel: Fact class. C) Synthesis of Eact and Fact analogs (see Materials and Methods).