{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T23:09:11Z","timestamp":1783120151925,"version":"3.54.6"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":46,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Fondazione Telethon","doi-asserted-by":"publisher","award":["TMLGCBX16TT"],"award-info":[{"award-number":["TMLGCBX16TT"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","award":["GALIET17G0"],"award-info":[{"award-number":["GALIET17G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000735","name":"University of Cambridge","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008459","name":"University of Calgary","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006920","name":"University of Pennsylvania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pharmacological modulators of the Ca2+ signaling cascade are important research tools and may translate into novel therapeutic strategies for a series of human diseases. We carried out a screening of a maximally diverse chemical library using the Ca2+-sensitive Cl\u2212 channel TMEM16A as a functional readout. We found compounds that were able to potentiate UTP-dependent TMEM16A activation. Mechanism of action of these compounds was investigated by a panel of assays that looked at intracellular Ca2+ mobilization triggered by extracellular agonists or by caged-IP3 photolysis, PIP2 breakdown by phospholipase C, and ion channel activity on nuclear membrane. One compound appears as a selective potentiator of inositol triphosphate receptor type 1 (ITPR1) with a possible application for some forms of spinocerebellar ataxia. A second compound is instead a potentiator of the P2RY2 purinergic receptor, an activity that could promote fluid secretion in dry eye and chronic obstructive respiratory diseases.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgac288","type":"journal-article","created":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T02:53:15Z","timestamp":1670640795000},"source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological potentiators of the calcium signaling cascade identified by high-throughput screening"],"prefix":"10.1093","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9350-1191","authenticated-orcid":false,"given":"Michele","family":"Genovese","sequence":"first","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM) , Pozzuoli, 80078 Naples , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Guidone","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine (TIGEM) , 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