ArticleNature communications2025
Identification of a binding site for small molecule inhibitors targeting human TRPM4.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Signatures of micropeptides encoded by lncRNAs in cancer progression and metastasis.British journal of cancer · 2026Article
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.Nature communications · 2026Article
- Role of TRPM4 ion channel in pediatric arrhythmic syndromes.World journal of clinical pediatrics · 2026Review
- Temperature-dependent ligand relocation reveals plasticity of TRPM4 inhibition.bioRxiv : the preprint server for biology · 2026Article
- Temperature and intrinsic CaNature structural & molecular biology · 2026Article
- CryoWriter: a robotic solution for improved Cryo-EM grid preparation.Nature communications · 2026Article
- Potent Anthranilic Anilide-Based TRPM4 Channel Inhibitors Identified by a Structure-Activity Relationship Study.Journal of medicinal chemistry · 2026Article
- Necrosis by sodium overload: a potential mechanism for renal diseases associated with mitochondrial dysfunction.Cell death discovery · 2026Article
- Structural mechanism of Necrocide 1 activation of human TRPM4 that triggers necrosis by sodium overload.bioRxiv : the preprint server for biology · 2026Article
- A single allosteric site merges activation, modulation and inhibition in TRPM5.Nature chemical biology · 2026Article
- Noncanonical calcium-independent TRPM4 activation governs intestinal fluid homeostasis.Nature communications · 2026Article
- Structural biology of the TRPM4 channel: architecture, modulation, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- MAASTY: a (dis)ordered copolymer for structural determination of human membrane proteins in native nanodiscs.Nature communications · 2025Article
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- TRPM4 expression predicts prognosis and modulates the immune microenvironment in pancreatic adenocarcinoma.Scientific reports · 2025Article
- Deciphering the language of mingling lipids and proteins.Current opinion in structural biology · 2025Review
- Comprehensive Insights Into the Role of TRPM4 in Pan-Cancer Progression and Immune Regulation.ImmunoTargets and therapy · 2025Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug development targeting TRPM4. We determine three cryo-EM structures of full-length human TRPM4 embedded in native lipid nanodiscs without inhibitor, bound to NBA, and an anthranilic acid derivative, IBA. We found that the small molecules NBA and IBA were bound in a pocket formed between the S3, S4, and TRP helices and the S4-S5 linker of TRPM4. Our structural data and results from patch clamp experiments enable validation of a binding site for small molecule inhibitors, paving the way for further drug development targeting TRPM4.
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Registered trials
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