Miner, Kent published the artcileDrug repurposing: the anthelmintics niclosamide and nitazoxanide are potent TMEM16A antagonists that fully bronchodilate airways, Synthetic Route of 55981-09-4, the main research area is asthma niclosamide nitazoxanide TMEM16A smooth muscle depolarization contraction; TMEM16A antagonist; airway smooth muscle (ASM); bronchodilator; calcium-activated chloride channel; desensitization; drug repositioning; niclosamide; nitazoxanide.
There is an unmet need in severe asthma where approx. 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 addnl. 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 mol. target for these drugs and thus provide fresh insights into their mechanism for the treatment of these disorders in addition to respiratory disease.
Frontiers in Pharmacology published new progress about Anthelmintics. 55981-09-4 belongs to class esters-buliding-blocks, name is 2-((5-Nitrothiazol-2-yl)carbamoyl)phenyl acetate, and the molecular formula is C12H9N3O5S, Synthetic Route of 55981-09-4.
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics