Reactome | ANO1 inhibitors bind ANO1

ANO1 inhibitors bind ANO1

Stable Identifier

R-HSA-9659611

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

Calcium-activated chloride channels (CaCCs) are ubiquitously expressed and implicated in physiological processes such as sensory transduction, fertilization, epithelial secretion, and smooth muscle contraction. Anoctamin 1 (ANO1, TMEM16A) is a Ca(2+)-activated Cl(-) channel (CACC) expressed in smooth muscle and epithelial cells and highly expressed in interstitial cells of Cajal throughout the GI tract (Sanders et al. 2012). ANO1, amongst other ion channels, generates electrical activity that drives contractility in the GI tract (Yang et al. 2008, Scudieri et al. 2012). Crofelemer (trade name Mytesi) is a purified proanthocyanidin oligomer extracted from the bark latex of Croton lechlerifor used for the treatment of diarrhoea associated with anti-HIV drugs (Yeo et al. 2013). Crofelemer was found to strongly inhibit the intestinal ANO1 by a voltage-independent inhibition mechanism (Tradtrantip et al. 2010). ANO1 blockers like niflumic acid have been shown to block slow waves, which produce motility, in the human intestine (Strege et al. 2015). Anthracene-9-carboxylic acid (A9C) is an open ANO1 channel blocker and gating modifier (Ta et al. 2016).

Literature References

PubMed ID	Title	Journal	Year
19808995	Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels Verkman, AS, Tradtrantip, L, Namkung, W	Mol. Pharmacol.	2010
26359375	A novel exon in the human Ca2+-activated Cl- channel Ano1 imparts greater sensitivity to intracellular Ca2 Farrugia, G, Bernard, CE, Linden, DR, Strege, PR, Mazzone, A, Gibbons, SJ, Beyder, A	Am. J. Physiol. Gastrointest. Liver Physiol.	2015
26562072	Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker Garnett, H, Rorsman, NJ, Tammaro, P, Ta, CM, Adomaviciene, A	Br. J. Pharmacol.	2016
23616951	Crofelemer, a novel antisecretory agent approved for the treatment of HIV-associated diarrhea Yeo, QM, Tucker, A, Crutchley, R, Garey, KW, Cottreau, J	Drugs Today	2013