NPD-039

NPD-039 (compound 9) inhibits full-length TbrPDEB1 with a K_i of 99 nM; the pK_i values for TbrPDEB1 and hPDE4B1 are 7.0 and 5.7, respectively, conferring a 19-fold preference for TbrPDEB1^[2].
The co-crystal structure of NPD-039 in complex with TbrPDEB1 is determined at a resolution of 2.0 Å; the (4aR,8aS)-enantiomer is observed in the crystal, with its methoxyphenyl group occupying the hydrophobic clamp and targeting the P-pocket, while its glycinamide tail forms direct hydrogen bonds with Tyr845^Q2.36 and Glu869^Q2.45, and forms hydrogen-bonding interactions with Thr841^Q2.33/Met861^S.40 and Leu870^Q2.46/Gln874^Q.50 via water molecules^[2].
NPD-039 (0.25-64 μM; 72 h) exhibits cytotoxicity against MRC-5 SV2, with a CC₅₀ of 35 μM^[2].
NPD-039 (0.25-64 μM; 72 h) inhibits the growth of T. brucei Squib-427 parasites with an IC₅₀ of 6.7 μM^[2].
NPD-039 exhibits an anti-T. brucei phenotype similar to that of NPD-008 in the T. brucei cytokinesis assay^[2].

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