ArticleMolecular pharmacology2013
MONNA, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1.
Article in Molecular pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 124 citations in OpenAlex.
- TMEM16A Contributes to Calcium-Activated Chloride Currents and Membrane Potential Changes in the Mouse Oocyte.Journal of cellular physiology · 2026Article
- Research and optimization of screening strategy for calcium-activated chloride channel modulators guided by electrophysiological characteristics.Scientific reports · 2026Article
- Tamsulosin ameliorates bone loss by inhibiting the release of ClProceedings of the National Academy of Sciences of the United States of America · 2025Article
- ANO1: central role and clinical significance in non-neoplastic and neoplastic diseases.Frontiers in immunology · 2025Review
- The epsilon toxin from Clostridium perfringens stimulates calcium-activated chloride channels, generating extracellular vesicles in Xenopus oocytes.Pharmacology research & perspectives · 2024Article
- Involvement of ANO1 currents in pacemaking of PDGFRα-positive specialised smooth muscle cells in rat caudal epididymis.Cell and tissue research · 2024Article
- Anticancer Effect of Hemin through ANO1 Inhibition in Human Prostate Cancer Cells.International journal of molecular sciences · 2024Article
- Hijacking of internal calcium dynamics by intracellularly residing viral rhodopsins.Nature communications · 2024Article
- Function and Regulation of the Calcium-Activated Chloride Channel Anoctamin 1 (TMEM16A).Handbook of experimental pharmacology · 2024Article
- Structure and Function of Calcium-Activated Chloride Channels and Phospholipid Scramblases in the TMEM16 Family.Handbook of experimental pharmacology · 2024Review
- ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.The Journal of general physiology · 2023Article
- Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated CaThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- An activator of voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- TMEM16A as a potential treatment target for head and neck cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Inhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC.Nature communications · 2022Article
- The Ca2+-gated channel TMEM16A amplifies capillary pericyte contraction and reduces cerebral blood flow after ischemia.The Journal of clinical investigation · 2022Article
- Evidence for tetrodotoxin-resistant spontaneous myogenic contractions of mouse isolated stomach that are dependent on acetylcholine.British journal of pharmacology · 2022Article
- EnterotoxigenicPathogens (Basel, Switzerland) · 2022Review
- Positive modulation of the TMEM16B mediated currents by TRPV4 antagonist.Biochemistry and biophysics reports · 2021Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a --NO₂ group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC₅₀ < 10 μM. The most potent blocker, N-((4-methoxy)-2-naphthyl)-5-nitroanthranilic acid (MONNA), had an IC₅₀ of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10∼30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.
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