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We previously identified the acylaminocycloalkylthiophene class of TMEM16A inhibitors, which, following medicinal chemistry, gave analog 2\u2010bromodifluoroacetylamino\u20105,6,7,8\u2010tetrahydro\u20104\n                    <jats:italic>H<\/jats:italic>\n                    \u2010cyclohepta[\n                    <jats:italic>b<\/jats:italic>\n                    ]thiophene\u20103\u2010carboxylic acid\n                    <jats:italic>o<\/jats:italic>\n                    \u2010tolylamide (TM\n                    <jats:sub>inh<\/jats:sub>\n                    \u201023) with 30 nM half\u2010maximal inhibitory concentration. Here, we tested the efficacy of TMinh\u201023 for inhibition of GI motility in mice. In isolated murine gastric antrum, TM\n                    <jats:sub>inh<\/jats:sub>\n                    \u201023 strongly inhibited spontaneous and carbachol\u2010stimulated rhythmic contractions. Pharmacokinetic analysis showed predicted therapeutic concentrations of TM\n                    <jats:sub>inh<\/jats:sub>\n                    \u201023 for at least 4 h following a single oral or intraperitoneal dose at 10 mg\/kg. Gastric emptying, as assessed following an oral bolus of phenol red or independently by [\n                    <jats:sup>99m<\/jats:sup>\n                    Tc]\u2010diethylenetriamine pentaacetic acid scintigraphy, was reduced by TM\n                    <jats:sub>inh<\/jats:sub>\n                    \u201023 by \u223c60% at 20 min. Interestingly, there was little effect of TMinh\u201023 on baseline whole\u2010gut transit time or time to diarrhea induced by castor oil. Consequent to the delay in gastric emptying, TM\n                    <jats:sub>inh<\/jats:sub>\n                    \u201023 administration significantly reduced the elevation in blood sugar in mice following an oral but not intraperitoneal glucose load. These results provide pharmacological evidence for involvement of TMEM16A in gastric emptying and suggest the utility of TMEM16A inhibition in disorders of accelerated gastric emptying, such as dumping syndrome, and potentially for improving glucose tolerance in diabetes mellitus\/metabolic syndrome and enhancing satiety in obesity.\u2014Cil, O., Anderson, M. O., Yen, R., Kelleher, B., Huynh, T. L., Seo, Y., Nilsen, S. P., Turner, J. R., Verkman, A. S. Slowed gastric emptying and improved oral glucose tolerance produced by a nanomolar\u2010potency inhibitor of calcium\u2010activated chloride channel TMEM16A. FASEB J. 33, 11247\u201311257 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201900858r","type":"journal-article","created":{"date-parts":[[2019,7,12]],"date-time":"2019-07-12T17:09:51Z","timestamp":1562951391000},"page":"11247-11257","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Slowed gastric emptying and improved oral glucose tolerance produced by a nanomolar\u2010potency inhibitor of calcium\u2010activated chloride channel TMEM16A"],"prefix":"10.1096","volume":"33","author":[{"given":"Onur","family":"Cil","sequence":"first","affiliation":[{"name":"Department of Medicine and Physiology University of California San Francisco California USA"},{"name":"Department of Pediatrics University of California San Francisco California 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