Optimization of PDE3A Modulators for SLFN12-Dependent Cancer Cell Killing.

ACS Med Chem Lett

Authors	Timothy Lewis Luc de Waal Xiaoyun Wu Willmen Youngsaye Antje Wengner Charlotte Kopitz Martin Lange Stefan Gradl Manuel Ellermann Philip Lienau Stuart Schreiber Heidi Greulich Matthew Meyerson
Abstract	6-(4-(Diethylamino)-3-nitrophenyl)-5-methyl-4,5-dihydropyridazin-3(2)-one, or , 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 analogs was evaluated using a phenotypic viability assay, resulting in several compounds with suitable pharmacokinetic properties for analysis. One of these compounds, , was active in an SK-MEL-3 xenograft model of cancer.
Year of Publication	2019
Journal	ACS Med Chem Lett
Volume	10
Issue	11
Pages	1537-1542
Date Published	2019 Nov 14
ISSN	1948-5875
DOI	10.1021/acsmedchemlett.9b00360
PubMed ID	31749907
PubMed Central ID	PMC6862344
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