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Anoctamin-1 (ANO1, also known as TMEM16A) is a transmembrane protein that forms a voltage- and calcium-activated chloride channel, mainly conducting chloride and, to a lesser extent, bicarbonate and iodide ions[1][4][5]. It is widely expressed in epithelial and smooth muscle tissues, as well as in interstitial cells of Cajal (pacemakers of the gut), and is essential for diverse physiological processes including fluid secretion, muscle contraction, cell proliferation, and neuronal signaling[1][4][5]. ANO1 has major pathophysiological roles: it is overexpressed in several cancers (especially GISTs, where DOG1 immunostaining is diagnostic), contributes to cyst formation in polycystic kidney disease, and is implicated in airway diseases and sensory pain pathways[2][4][5]. While no approved drugs specifically target ANO1 in the clinic, it is the focus of substantial drug discovery efforts for new modulators in oncology, airway disorders, and gastrointestinal motility disorders[4][5].
ANO1 antagonists/inhibitors block calcium-activated chloride currents, reducing epithelial secretion and smooth muscle activity This can impact cell proliferation, limit tumor growth (in cancer), reduce mucus secretion (in airway/CF), and modify excitability (in pain pathways)
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