ArticleProceedings of the National Academy of Sciences of the United States of America2025
Tamsulosin ameliorates bone loss by inhibiting the release of Cl
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- Paroxetine as a Therapeutic Agent in Inflammatory Osteolysis: Mechanistic Insights and Efficacy.Drug design, development and therapy · 2026Article
- Osteoporosis diagnosis and ingredients of prescription medications: a population-based study.Frontiers in pharmacology · 2025Article
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Authors and funding
20 authors.
Funding
Abstract
TMEM16A, a key calcium-activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high-resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.93 Å. Tamsulosin wedges itself into a pocket within the extracellular domain of TMEM16A, surrounded by α1-α2, α5-α6, and α9-α10 loops. This binding stabilizes a transient preopen conformation of TMEM16A, which is activated by Ca
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