ArticleJournal of medicinal chemistry2013
Structure-activity relationship of adenosine 5'-diphosphoribose at the transient receptor potential melastatin 2 (TRPM2) channel: rational design of antagonists.
Article in Journal of medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Design, structure-based optimization and antiviral evaluation of potent inhibitors for the macrodomain Mac1 of SARS-CoV-2.Nature communications · 2026Article
- Ugi multicomponent reactions of optically active aldehydes and chiral aminoindanols: diastereoselective synthesis of bisamides relevant to SARS-CoV-2 Mpro inhibitors.Organic & biomolecular chemistry · 2026Article
- Pathophysiological significance of the TRPM2 ion channel as a potential target in cancer, neurological disorders, and ischemia/reperfusion injury.Pharmacological research · 2026Review
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Synthesis of New DltA Inhibitors and Their Application as Adjuvant Antibiotics to Re-Sensitize Methicillin-ResistantMolecules (Basel, Switzerland) · 2025Article
- [Advances in the development of transient receptor potential melastatin 2 channel inhibitors].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Review
- Design and synthesis of a library of C8-substituted sulfamidoadenosines to probe bacterial permeability.Bioorganic & medicinal chemistry letters · 2024Article
- 2'-deoxy-ADPR activates human TRPM2 faster than ADPR and thereby induces higher currents at physiological CaFrontiers in immunology · 2024Article
- Article
- Transient Receptor Potential (TRP) Channels in Pain, Neuropsychiatric Disorders, and Epilepsy.International journal of molecular sciences · 2023Review
- Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7.Frontiers in cell and developmental biology · 2023Review
- Synthesis and Characterization of NUC-7738, an Aryloxy Phosphoramidate of 3'-Deoxyadenosine, as a Potential Anticancer Agent.Journal of medicinal chemistry · 2022Article
- The crystal structure of TRPM2 MHR1/2 domain reveals a conserved ZnProtein science : a publication of the Protein Society · 2022Article
- cADPR Does Not Activate TRPM2.International journal of molecular sciences · 2022Article
- TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention.Channels (Austin, Tex.) · 2021Review
- TRP channels in COVID-19 disease: Potential targets for prevention and treatment.Chemico-biological interactions · 2021Review
- TRPM2 Non-Selective Cation Channels in Liver Injury Mediated by Reactive Oxygen Species.Antioxidants (Basel, Switzerland) · 2021Review
- The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy.International journal of molecular sciences · 2021Review
- Two Decades of Evolution of Our Understanding of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel.Life (Basel, Switzerland) · 2021Review
- Enhanced production of cordycepin inBiotechnology reports (Amsterdam, Netherlands) · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Adenosine 5'-diphosphoribose (ADPR) activates TRPM2, a Ca(2+), Na(+), and K(+) permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure-activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 μM), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfamate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca(2+) signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.