Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing

6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one, or DNMDP, potently and selectively inhibits phosphodiesterases 3A and 3B (PDE3A and PDE3B) and kills cancer cells by inducing PDE3A/B interactions with SFLN12. The structure–activity relationship (SAR) of DNMDP analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for in vivo analysis. One of...