Matches in SemOpenAlex for { <https://semopenalex.org/work/W2952473760> ?p ?o ?g. }
- W2952473760 abstract "There is an unmet need in severe asthma where approximately 40% of patients exhibit poor β-agonist responsiveness, suffer daily symptoms and show frequent exacerbations. Antagonists of the Ca2+-activated Cl- channel, TMEM16A, offers a new mechanism to bronchodilate airways and block the multiple contractiles operating in severe disease. To identify TMEM16A antagonists we screened a library of ∼580,000 compounds. The anthelmintics niclosamide, nitazoxanide, and related compounds were identified as potent TMEM16A antagonists that blocked airway smooth muscle depolarization and contraction. To evaluate whether TMEM16A antagonists resist use- and inflammatory-desensitization pathways limiting β-agonist action, we tested their efficacy under harsh conditions using maximally contracted airways or airways pretreated with a cytokine cocktail. Stunningly, TMEM16A antagonists fully bronchodilated airways, while the β-agonist isoproterenol showed only partial effects. Thus, antagonists of TMEM16A and repositioning of niclosamide and nitazoxanide represent an important additional treatment for patients with severe asthma and COPD that is poorly controlled with existing therapies. It is of note that drug repurposing has also attracted wide interest in niclosamide and nitazoxanide as a new treatment for cancer and infectious disease. For the first time we identify TMEM16A as a molecular target for these drugs and thus provide fresh insights into their mechanism for the treatment of these disorders in addition to respiratory disease." @default.
- W2952473760 created "2019-06-27" @default.
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- W2952473760 date "2019-02-14" @default.
- W2952473760 modified "2023-10-16" @default.
- W2952473760 title "Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways" @default.
- W2952473760 cites W1524900861 @default.
- W2952473760 cites W1536852491 @default.
- W2952473760 cites W1613323871 @default.
- W2952473760 cites W1716400262 @default.
- W2952473760 cites W1835419280 @default.
- W2952473760 cites W1841157386 @default.
- W2952473760 cites W1894088205 @default.
- W2952473760 cites W1912463191 @default.
- W2952473760 cites W1956352664 @default.
- W2952473760 cites W1964669406 @default.
- W2952473760 cites W1967510354 @default.
- W2952473760 cites W1969791503 @default.
- W2952473760 cites W1972192702 @default.
- W2952473760 cites W1972212283 @default.
- W2952473760 cites W1976550936 @default.
- W2952473760 cites W1981193117 @default.
- W2952473760 cites W1988591299 @default.
- W2952473760 cites W1989757776 @default.
- W2952473760 cites W1994132777 @default.
- W2952473760 cites W1996708800 @default.
- W2952473760 cites W2002141156 @default.
- W2952473760 cites W2005402925 @default.
- W2952473760 cites W2006050756 @default.
- W2952473760 cites W2008552098 @default.
- W2952473760 cites W2008964034 @default.
- W2952473760 cites W2010131036 @default.
- W2952473760 cites W2013105339 @default.
- W2952473760 cites W2014374660 @default.
- W2952473760 cites W2018160598 @default.
- W2952473760 cites W2021332114 @default.
- W2952473760 cites W2027353006 @default.
- W2952473760 cites W2028005568 @default.
- W2952473760 cites W2030389672 @default.
- W2952473760 cites W2032921167 @default.
- W2952473760 cites W2038606037 @default.
- W2952473760 cites W2038731679 @default.
- W2952473760 cites W2041339949 @default.
- W2952473760 cites W2043398720 @default.
- W2952473760 cites W2043536877 @default.
- W2952473760 cites W2049314578 @default.
- W2952473760 cites W2058392358 @default.
- W2952473760 cites W2060891750 @default.
- W2952473760 cites W2061800084 @default.
- W2952473760 cites W2064524507 @default.
- W2952473760 cites W2066968375 @default.
- W2952473760 cites W2072130252 @default.
- W2952473760 cites W2078571865 @default.
- W2952473760 cites W2078612273 @default.
- W2952473760 cites W2079357498 @default.
- W2952473760 cites W2085178645 @default.
- W2952473760 cites W2086627198 @default.
- W2952473760 cites W2092868876 @default.
- W2952473760 cites W2094582218 @default.
- W2952473760 cites W2095655618 @default.
- W2952473760 cites W2096272013 @default.
- W2952473760 cites W2096465161 @default.
- W2952473760 cites W2096864778 @default.
- W2952473760 cites W2107018762 @default.
- W2952473760 cites W2111580238 @default.
- W2952473760 cites W2111751035 @default.
- W2952473760 cites W2112290804 @default.
- W2952473760 cites W2113549181 @default.