ENPP1 inhibitor QPS1 (QPS1) is a potent, selective non-competitive inhibitor of Ectonucleotide pyrophosphatase/PDE1 (NPP1, ENPP1) with Ki of 59.3 nM.
QPS1 also significantly inhibited the K121Q NPP1 gene variant with Ki of 59.2 nM.
QPS1 did not significantly alter the activity of other nucleotide metabolizing ectoenzymes expressed at the cell surface, namely NPP3, NTPDases (1–3), ecto-5′-nucleotidase and ALP.
QPS1 (10 uM) prevented phosphate-induced mineralization of VICs and lowered the rise of osteogenic genes as expected for NPP1 inhibition.
In ENPP1 null cells, QPS1 also increased intracellular cGAMP and decreased extracellular cGAMP concentrations, suggesting that it blocks the cGAMP exporter.
QPS1) inhibits extracellular cGAMP degradation in cells overexpressing ENPP1.
