Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing.
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ABSTRACT:
SUBMITTER: Lewis TA
PROVIDER: S-EPMC6862344 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing.
Lewis Timothy A TA de Waal Luc L Wu Xiaoyun X Youngsaye Willmen W Wengner Antje A Kopitz Charlotte C Lange Martin M Gradl Stefan S Ellermann Manuel M Lienau Philip P Schreiber Stuart L SL Greulich Heidi H Meyerson Matthew M
ACS medicinal chemistry letters 20191018 11
6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2<i>H</i>)-one, or <b>DNMDP</b>, 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 <b>DNMDP</b> analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for <i>in vivo</i> analysis. One of these compounds, <b>BRD950 ...[more]
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