ArticleChemMedChem2011
Benzyl and naphthalene methylphosphonic acid inhibitors of autotaxin with anti-invasive and anti-metastatic activity.
Article in ChemMedChem, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 66 citations in OpenAlex.
- Synthesis of Autotaxin-Inhibiting Lipid Nanoparticles to Regulate Autophagy and Inflammatory Responses in Activated Macrophages.Tissue engineering and regenerative medicine · 2025Article
- Structure-Based Discovery of MolPort-137: A Novel Autotaxin Inhibitor That Improves Paclitaxel Efficacy.International journal of molecular sciences · 2025Article
- Deleting autotaxin in LysM+ myeloid cells impairs innate tumor immunity in models of metastatic melanoma.iScience · 2024Article
- One-Pot Formal Carboradiofluorination of Alkenes: A Toolkit for Positron Emission Tomography Imaging Probe Development.Journal of the American Chemical Society · 2023Article
- Review
- Review
- Prometastatic Effect of ATX Derived from Alveolar Type II Pneumocytes and B16-F10 Melanoma Cells.Cancers · 2022Article
- Design and Development of Autotaxin Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Endogenous Anti-Cancer Candidates in GPCR, ER Stress, and EMT.Biomedicines · 2020Review
- Molecular modelling guided design, synthesis and QSAR analysis of new small molecule non-lipid autotaxin inhibitors.Bioorganic chemistry · 2020Article
- Pleotropic Roles of Autotaxin in the Nervous System Present Opportunities for the Development of Novel Therapeutics for Neurological Diseases.Molecular neurobiology · 2020Review
- Review
- Osteoclast-Derived Autotaxin, a Distinguishing Factor for Inflammatory Bone Loss.Arthritis & rheumatology (Hoboken, N.J.) · 2019Article
- Review
- Lysophosphatidic acid type 2 receptor agonists in targeted drug development offer broad therapeutic potential.Journal of lipid research · 2019Review
- Regulation of tumor cell - Microenvironment interaction by the autotaxin-lysophosphatidic acid receptor axis.Advances in biological regulation · 2019Review
- Platelets, autotaxin and lysophosphatidic acid signalling: win-win factors for cancer metastasis.British journal of pharmacology · 2018Review
- Highly Potent Non-Carboxylic Acid Autotaxin Inhibitors Reduce Melanoma Metastasis and Chemotherapeutic Resistance of Breast Cancer Stem Cells.Journal of medicinal chemistry · 2017Article
- Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma.Bioorganic & medicinal chemistry · 2015Article
- The Autotaxin-Lysophosphatidic Acid Axis Modulates Histone Acetylation and Gene Expression during Oligodendrocyte Differentiation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Autotaxin (ATX, NPP2) is a member of the nucleotide pyrophosphate phosphodiesterase enzyme family. ATX catalyzes the hydrolytic cleavage of lysophosphatidylcholine (LPC) by lysophospholipase D activity, which leads to generation of the growth-factor-like lipid mediator lysophosphatidic acid (LPA). ATX is highly upregulated in metastatic and chemotherapy-resistant carcinomas and represents a potential target to mediate cancer invasion and metastasis. Herein we report the synthesis and pharmacological characterization of ATX inhibitors based on the 4-tetradecanoylaminobenzylphosphonic acid scaffold, which was previously found to lack sufficient stability in cellular systems. The new 4-substituted benzylphosphonic acid and 6-substituted naphthalen-2-ylmethylphosphonic acid analogues block ATX activity with K(i) values in the low micromolar to nanomolar range against FS3, LPC, and nucleotide substrates through a mixed-mode inhibition mechanism. None of the compounds tested inhibit the activity of related enzymes (NPP6 and NPP7). In addition, the compounds were evaluated as agonists or antagonists of seven LPA receptor (LPAR) subtypes. Analogues 22 and 30 b, the two most potent ATX inhibitors, inhibit the invasion of MM1 hepatoma cells across murine mesothelial and human vascular endothelial monolayers in vitro in a dose-dependent manner. The average terminal half-life for compound 22 is 10±5.4 h and it causes a long-lasting decrease in plasma LPA levels. Compounds 22 and 30 b significantly decrease lung metastasis of B16-F10 syngeneic mouse melanoma in a post-inoculation treatment paradigm. The 4-substituted benzylphosphonic acids and 6-substituted naphthalen-2-ylmethylphosphonic acids described herein represent new lead compounds that effectively inhibit the ATX-LPA-LPAR axis both in vitro and in vivo.
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What Socratic holds
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 Socratic graph.