Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing.
Basic Information
ID: ALA5260844
Journal: ACS Med Chem Lett
Title: Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing.
Authors: Lewis TA, de Waal L, Wu X, Youngsaye W, Wengner A, Kopitz C, Lange M, Gradl S, Ellermann M, Lienau P, Schreiber SL, Greulich H, Meyerson M.
Abstract: 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 these compounds, BRD9500, was active in an SK-MEL-3 xenograft model of cancer.
CiteXplore: 31749907
DOI: 10.1021/acsmedchemlett.9b00360
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