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Echinobase
ECB-ART-41047
Nat Chem Biol 2009 Apr 01;54:220-6. doi: 10.1038/nchembio.150.
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Identification of a chemical probe for NAADP by virtual screening.

Naylor E , Arredouani A , Vasudevan SR , Lewis AM , Parkesh R , Mizote A , Rosen D , Thomas JM , Izumi M , Ganesan A , Galione A , Churchill GC .


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Research into the biological role of the Ca(2+)-releasing second messenger NAADP (nicotinic acid adenine dinucleotide phosphate) has been hampered by a lack of chemical probes. To find new chemical probes for exploring NAADP signaling, we turned to virtual screening, which can evaluate millions of molecules rapidly and inexpensively. We used NAADP as the query ligand to screen the chemical library ZINC for compounds with similar three-dimensional shape and electrostatic properties. We tested the top-ranking hits in a sea urchin egg bioassay and found that one hit, Ned-19, blocks NAADP signaling at nanomolar concentrations. In intact cells, Ned-19 blocked NAADP signaling and fluorescently labeled NAADP receptors. Moreover, we show the utility of Ned-19 as a chemical probe by using it to demonstrate that NAADP is a key causal link between glucose sensing and Ca(2+) increases in mouse pancreatic beta cells.

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Genes referenced: LOC100887844 LOC574780 LOC576539


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References [+] :
Aarhus, Activation and inactivation of Ca2+ release by NAADP+. 1996, Pubmed, Echinobase