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ACS Med Chem Lett DOI:10.1021/acsmedchemlett.9b00360

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

Publication TypeJournal Article
Year of Publication2019
AuthorsLewis, 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
JournalACS Med Chem Lett
Volume10
Issue11
Pages1537-1542
Date Published2019 Nov 14
ISSN1948-5875
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.

DOI10.1021/acsmedchemlett.9b00360
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31749907?dopt=Abstract

Alternate JournalACS Med Chem Lett
PubMed ID31749907
PubMed Central IDPMC6862344