NPD-008

NPD-008 potently inhibits T. cruzi of different morphological forms and strains in vitro, with an EC₅₀ value of 9.7 μM against intracellular amastigotes and an EC₅₀ value of 6.6 μM against trypomastigotes^[1].
NPD-008 exhibits moderate in vitro activity against intracellular amastigotes of Leishmania amazonensis and Leishmania infantum^[1].
NPD-008 (24-96 h) potently inhibits multiple forms of Trypanosoma cruzi, with the highest activity against bloodstream trypomastigotes (EC₅₀ = 6.6 μM), and exhibits low cytotoxicity to mammalian cells, thus conferring a favorable selectivity index^[3].
NPD-008 (48-72 h) exhibits moderate leishmanicidal activity against the in vitro promastigotes of Leishmania amazonensis (EC₅₀ = 14.9 μM) and the intracellular amastigotes of Leishmania infantum (EC₅₀ = 12.5 μM)^[3].
NPD-008 (10 μM; 6-24 h) induces progressive cytokinesis defects and morphological degeneration in bloodstream-form Trypanosoma brucei parasites over a 24-hour incubation period^[4].
NPD-008 (compound 10) (2.5 h) increases intracellular and extracellular cAMP levels in bloodstream trypomastigotes of the Trypanosoma cruzi Y strain (DTU II)^[5].
NPD-008 (24 h) exerts an inhibitory effect on bloodstream trypomastigotes of the T. cruzi Y strain, with an EC₅₀ of 6.6 μM after 24 h of incubation^[6].
NPD-008 potently inhibits recombinant TbrPDEB1 with a K_i value of 100 nM and exhibits 10-fold selectivity over hPDE4B1; its (4aR,8aS)-enantiomer is 100-fold more potent against TbrPDEB1 and shows 16-fold selectivity over hPDE4B1^[2].
NPD-008 (compound 8) binds to the catalytic domain of TbrPDEB1 in the (4aR,8aS) configuration. Its glycinamide tail targets the parasite-specific P-pocket, while simultaneously occupying the conserved PDE hydrophobic clamp and interacting with Gln874Q.50^[2].
NPD-008 (100 nM-10000 nM) increases intracellular cAMP levels in bloodstream-form T. brucei in a dose-dependent manner, with a significant effect observed at a concentration of 10 μM after 5 h of incubation^[2].
NPD-008 exhibits cytotoxicity against human MRC-5 cells, with a CC₅₀ of 36 μM^[2].
NPD-008 (2.5 h) induces a dose-dependent increase in intracellular cAMP levels in both Trypanosoma cruzi amastigotes and bloodstream trypomastigotes, and elevates extracellular cAMP levels in cultures of bloodstream trypomastigotes, confirming its targeted inhibitory effect on phosphodiesterases^[3].
NPD-008 induces rapid ultrastructural changes in both blood trypomastigotes (rounded morphology) and epimastigotes (shortened cell body) of Trypanosoma cruzi within 15 minutes of treatment at a concentration of 1× EC₅₀^[3].
NPD-008 (10 μM; 6-24 h) inhibits the activity of bloodstream-form T. brucei with an IC₅₀ of 5.5 μM. It also disrupts cellular structure and cytokinesis, and induces abnormal cell morphology and the formation of multinucleated cells after 24 h of incubation at 10 μM^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.