Target intelligence / Profile preview

Anoctamin-1 channel (ANO1)

Target
ANO1
Molecular classification
Ion channel, Calcium-activated chloride channel, Transmembrane protein
01

Overview

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].

Other names
TMEM16ADOG1 (Discovered On Gastrointestinal stromal tumors 1)ORAOV2TAOS2Transmembrane member 16A
02

Mechanism of action

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)

03

Biological functions

Transepithelial anion (chloride and bicarbonate) transportSmooth muscle contractionCell proliferationCell migrationCell survivalElectrical pacemaker activity in gastrointestinal tractSecretion (in glands/epithelia)Neuronal excitation
04

Disease associations

Cancer (notably gastrointestinal stromal tumors, oral cancer, glioblastoma, etc.)Polycystic kidney diseaseCystic fibrosis (supporting mucus secretion)Gastrointestinal motility disordersAirway diseases (asthma, chronic obstructive pulmonary disease)Pain disorders (neuropathic pain, chronic pain)
05

Safety considerations

Possible impairment of epithelial secretion (airways, glands)Effects on gastrointestinal motilityPotential cardiovascular effects due to roles in vascular toneTumorigenic risk modulation in vulnerable tissuesUnintended effects on sensory neurons or pain signaling
06

Interacting drugs

No widely approved drugs directly targeting ANO1, but experimental modulators include:

4 more in the full profile.

07

Biomarkers

DOG1 (ANO1 immunostaining) for diagnosis of gastrointestinal stromal tumors (GIST)ANO1 mRNA or protein overexpression as biomarker for certain tumors

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