ArticleLipids in health and disease2005
L-histidine inhibits production of lysophosphatidic acid by the tumor-associated cytokine, autotaxin.
Article in Lipids in health and disease, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- Design and Development of Autotaxin Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Structure-Based Discovery of Novel Chemical Classes of Autotaxin Inhibitors.International journal of molecular sciences · 2020Article
- Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer.Cancers · 2019Article
- Protective effects of voltage-gated calcium channel antagonists against zinc toxicity in SN56 neuroblastoma cholinergic cells.PloS one · 2018Article
- Discovery and synthetic optimization of a novel scaffold for hydrophobic tunnel-targeted autotaxin inhibition.Bioorganic & medicinal chemistry · 2016Article
- Vinyl sulfone analogs of lysophosphatidylcholine irreversibly inhibit autotaxin and prevent angiogenesis in melanoma.Bioorganic & medicinal chemistry · 2015Article
- A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis.PloS one · 2013Article
- Chemical evolution of autotaxin inhibitors.Chemical reviews · 2012Review
- Ligand-based autotaxin pharmacophore models reflect structure-based docking results.Journal of molecular graphics & modelling · 2011Article
- Autotaxin: its role in biology of melanoma cells and as a pharmacological target.Enzyme research · 2011Article
- Autotaxin inhibitors: a perspective on initial medicinal chemistry efforts.Expert opinion on therapeutic patents · 2010Article
- Aiming drug discovery at lysophosphatidic acid targets.British journal of pharmacology · 2010Review
- Phospholipase Cgamma activation drives increased production of autotaxin in endothelial cells and lysophosphatidic acid-dependent regression.Molecular and cellular biology · 2010Article
- ATX-LPA receptor axis in inflammation and cancer.Cell cycle (Georgetown, Tex.) · 2009Review
- Autotaxin.Cellular and molecular life sciences : CMLS · 2009Review
- Autotaxin structure-activity relationships revealed through lysophosphatidylcholine analogs.Bioorganic & medicinal chemistry · 2009Article
- Therapeutic potential of autotaxin/lysophospholipase d inhibitors.Current drug targets · 2008Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundAutotaxin (ATX, NPP-2), originally purified as a potent tumor cell motility factor, is now known to be the long-sought plasma lysophospholipase D (LPLD). The integrity of the enzymatic active site, including three crucial histidine moieties, is required for motility stimulation, as well as LPLD and 5'nucleotide phosphodiesterase (PDE) activities. Except for relatively non-specific chelation agents, there are no known inhibitors of the ATX LPLD activity.
resultsWe show that millimolar concentrations of L-histidine inhibit ATX-stimulated but not LPA-stimulated motility in two tumor cell lines, as well as inhibiting enzymatic activities. Inhibition is reversed by 20-fold lower concentrations of zinc salt. L-histidine has no significant effect on the Km of LPLD, but reduces the Vmax by greater than 50%, acting as a non-competitive inhibitor. Several histidine analogs also inhibit the LPLD activity of ATX; however, none has greater potency than L-histidine and all decrease cell viability or adhesion.
conclusionL-histidine inhibition of LPLD is not a simple stoichiometric chelation of metal ions but is more likely a complex interaction with a variety of moieties, including the metal cation, at or near the active site. The inhibitory effect of L-histidine requires all three major functional groups of histidine: the alpha amino group, the alpha carboxyl group, and the metal-binding imidazole side chain. Because of LPA's involvement in pathological processes, regulation of its formation by ATX may give insight into possible novel therapeutic approaches.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.