ArticleBioorganic & medicinal chemistry2009
Autotaxin structure-activity relationships revealed through lysophosphatidylcholine analogs.
Article in Bioorganic & medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Solid-phase microextraction of endogenous metabolites from intact tissue validated using a Biocrates standard reference method kit.Journal of pharmaceutical analysis · 2023Article
- Identification of a differential metabolite-based signature in patients with late-stage knee osteoarthritis.Osteoarthritis and cartilage open · 2022Article
- Synthesis and Evaluation of Antitumor Alkylphospholipid Prodrugs.Pharmaceutical research · 2020Article
- Prediction of preeclampsia risk in first time pregnant women: Metabolite biomarkers for a clinical test.PloS one · 2020Article
- Discovery and synthetic optimization of a novel scaffold for hydrophobic tunnel-targeted autotaxin inhibition.Bioorganic & medicinal chemistry · 2016Article
- Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma.Bioorganic & medicinal chemistry · 2015Article
- Autotaxin: structure-function and signaling.Journal of lipid research · 2014Review
- miR-203 regulates nociceptive sensitization after incision by controlling phospholipase A2 activating protein expression.Anesthesiology · 2012Article
- Insights into autotaxin: how to produce and present a lipid mediator.Nature reviews. Molecular cell biology · 2011Review
- Benzyl and naphthalene methylphosphonic acid inhibitors of autotaxin with anti-invasive and anti-metastatic activity.ChemMedChem · 2011Article
- Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid.Bioorganic & medicinal chemistry letters · 2010Article
- Aiming drug discovery at lysophosphatidic acid targets.British journal of pharmacology · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to form the bioactive lipid lysophosphatidic acid (LPA). LPA stimulates cell proliferation, cell survival, and cell migration and is involved in obesity, rheumatoid arthritis, neuropathic pain, atherosclerosis and various cancers, suggesting that ATX inhibitors have broad therapeutic potential. Product feedback inhibition of ATX by LPA has stimulated structure-activity studies focused on LPA analogs. However, LPA displays mixed mode inhibition, indicating that it can bind to both the enzyme and the enzyme-substrate complex. This suggests that LPA may not interact solely with the catalytic site. In this report we have prepared LPC analogs to help map out substrate structure-activity relationships. The structural variances include length and unsaturation of the fatty tail, choline and polar linker presence, acyl versus ether linkage of the hydrocarbon chain, and methylene and nitrogen replacement of the choline oxygen. All LPC analogs were assayed in competition with the synthetic substrate, FS-3, to show the preference ATX has for each alteration. Choline presence and methylene replacement of the choline oxygen were detrimental to ATX recognition. These findings provide insights into the structure of the enzyme in the vicinity of the catalytic site as well as suggesting that ATX produces rate enhancement, at least in part, by substrate destabilization.
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Identifiers
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.