ArticleJournal of medicinal chemistry2009
Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP).
Article in Journal of medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
54 citing papers in PubMed, 104 citations in OpenAlex.
- Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine.The Journal of biological chemistry · 2013Trial
- Enzyme-Responsive Chemiluminescent Probes Assembled with Iridium(III) Photosensitizers via Host-Guest Chemistry for Chemiluminescence-Induced Photodynamic Therapy.Journal of the American Chemical Society · 2026Article
- Bone morphogenetic proteins 4 and 7 increase human white and brown adipocyte thermogenic capacity.JCI insight · 2026Article
- Cryo-Structural Insights into Enzymatic Peptide Self-Assembly Driving Extrinsic Lytic Cell Death.Journal of the American Chemical Society · 2026Article
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- TNAP dephosphorylates phosphocholine and phosphoethanolamine and participates in triglyceride transport from the liver to the bloodstream.Communications biology · 2025Article
- Ectonucleotidase inhibitors: targeting signaling pathways for therapeutic advancement-an in-depth review.Purinergic signalling · 2025Review
- Accelerating Cellular Uptake with Unnatural Amino Acid for Inhibiting Immunosuppressive Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- [1, 8]-Naphthyridine derivatives as dual inhibitor of alkaline phosphatase and carbonic anhydrase.BMC chemistry · 2023Article
- In Vitro and In Vivo Pharmacological Profiles of DS-1211, a Novel Potent, Selective, and Orally Bioavailable Tissue-Nonspecific Alkaline Phosphatase Inhibitor.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- Enzymatic Delivery of Magnetic Nanoparticles into Mitochondria of Live Cells.ChemNanoMat : chemistry of nanomaterials for energy, biology and more · 2021Article
- Tissue-Nonspecific Alkaline Phosphatase (TNAP) as the Enzyme Involved in the Degradation of Nucleotide Analogues in the Ligand Docking and Molecular Dynamics Approaches.Biomolecules · 2021Article
- Enzymatic Assemblies of Thiophosphopeptides Instantly Target Golgi Apparatus and Selectively Kill Cancer Cells*.Angewandte Chemie (International ed. in English) · 2021Article
- Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells.International journal of molecular sciences · 2021Review
- Dynamic Continuum of Nanoscale Peptide Assemblies Facilitates Endocytosis and Endosomal Escape.Nano letters · 2021Article
- Hydrolysis of Extracellular ATP by Vascular Smooth Muscle Cells Transdifferentiated into Chondrocytes Generates PInternational journal of molecular sciences · 2021Article
- Astrocytes in the Ventrolateral Preoptic Area Promote Sleep.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Enzymatically Formed Peptide Assemblies Sequestrate Proteins and Relocate Inhibitors to Selectively Kill Cancer Cells.Angewandte Chemie (International ed. in English) · 2020Article
- Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
We report the characterization and optimization of drug-like small molecule inhibitors of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme critical for the regulation of extracellular matrix calcification during bone formation and growth. High-throughput screening (HTS) of a small molecule library led to the identification of arylsulfonamides as potent and selective inhibitors of TNAP. Critical structural requirements for activity were determined, and the compounds were subsequently profiled for in vitro activity and bioavailability parameters including metabolic stability and permeability. The plasma levels following subcutaneous administration of a member of the lead series in rat was determined, demonstrating the potential of these TNAP inhibitors as systemically active therapeutic agents to target various diseases involving soft tissue calcification. A representative member of the series was also characterized in mechanistic and kinetic studies.
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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.