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• W2083751011 abstract "Background and purpose: ARL 67156, 6-N,N-Diethyl-D-β-γ-dibromomethylene adenosine triphosphate, originally named FPL 67156, is the only commercially available inhibitor of ecto-ATPases. Since the first report on this molecule, various ectonucleotidases responsible for the hydrolysis of ATP at the cell surface have been cloned and characterized. In this work, we identified the ectonucleotidases inhibited by ARL 67156. Experimental approach: The effect of ARL 67156 on recombinant NTPDase1, 2, 3 & 8 (mouse and human), NPP1, NPP3 and ecto-5′-nucleotidase (human) have been evaluated. The inhibition of the activity of NTPDases (using the following substrates: ATP, ADP, UTP), NPPs (pnp-TMP, Ap3A) and ecto-5′-nucleotidase (AMP) was measured by colorimetric or HPLC assays. Key results: ARL 67156 was a weak competitive inhibitor of human NTPDase1, NTPDase3 and NPP1 with Ki of 11±3, 18±4 and 12±3 μM, respectively. At concentrations used in the literature (50–100 μM), ARL 67156 partially but significantly inhibited the mouse and human forms of these enzymes. NTPDase2, NTPDase8, NPP3 and ecto-5′-nucleotidase activities were less affected. Importantly, ARL 67156 was not hydrolysed by either human NTPDase1, 2, 3, 8, NPP1 or NPP3. Conclusions and implications: In cell environments where NTPDase1, NTPDase3, NPP1 or mouse NTPDase8 are present, ARL 67156 would prolong the effect of endogenously released ATP on P2 receptors. However, it does not block any ectonucleotidases efficiently when high concentrations of substrates are present, such as in biochemical, pharmacological or P2X7 assays. In addition, ARL 67156 is not an effective inhibitor of NTPDase2, human NTPDase8, NPP3 and ecto-5′-nucleotidase. British Journal of Pharmacology (2007) 152, 141–150; doi:10.1038/sj.bjp.0707361" @default.
• W2083751011 created "2016-06-24" @default.
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• W2083751011 date "2007-09-01" @default.
• W2083751011 modified "2023-10-14" @default.
• W2083751011 title "Specificity of the ecto-ATPase inhibitor ARL 67156 on human and mouse ectonucleotidases" @default.
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• W2083751011 doi "https://doi.org/10.1038/sj.bjp.0707361" @default.
• W2083751011 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1978278" @default.
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