Inhibition of ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) by compounds from fernandoa adenophylla (wall. ex G.Don) Steenis

Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is an enzyme that regulates several downstream pathways related to hydrolyses 2′,3′-cyclic GMP-AMP dinucleotide (2′,3′-cGAMP) signalling, and compounds targeting ENPP1 may find future applications in cancer and immunomodulation. In this work, 5 molecules were extracted from Fernandoa adenophylla (Wall. ex G.Don) Steenis and tested in vitro against the phosphodiesterase, highlighting methyl 1,2-dihydroxy-2-(3-methylbut-2-enyl)-3-oxoindene-1-carboxylate as the most potent inhibitor of the set. Computational techniques, including ligand-based simulations, molecular docking and machine learning-assisted toxicity predictions, further suggest that the compound may represent a promising lead in the context of ENPP1 inhibitors.