{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Waaler J"],"funding":["Academy of Finland","South-Eastern Norway Regional Health Authority","Kreftforeningen","Norges Forskningsr?d","Jane ja Aatos Erkon S??ti?","Sigrid Jus?liuksen S??ti?","Universitetet i Oslo"],"pagination":["6834-6846"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8008393"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["63(13)"],"pubmed_abstract":["Tankyrases 1 and 2 are central biotargets in the WNT/β-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and <i>trans-</i>cyclobutyl linker of the lead compound <b>1</b> were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC<sub>50</sub> inhibition in WNT/β<i>-</i>catenin signaling cellular reporter assay. The "],"journal":["Journal of medicinal chemistry"],"pubmed_title":["Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor."],"pmcid":["PMC8008393"],"funding_grant_id":["5803958","319299","2015012","16/00528-9","15/00779-2","262613","296226","2019090","267639","287063","294085"],"pubmed_authors":["Murthy S","Damen E","Lycke M","Krauss S","Waaler J","Leenders RGG","Nazare M","Wegert A","Lehtio L","Sowa ST","Galera-Prat A","Alam Brinch S","Nieczypor P","Aertssen S"],"additional_accession":[]},"is_claimable":false,"name":"Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor.","description":"Tankyrases 1 and 2 are central biotargets in the WNT/β-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and <i>trans-</i>cyclobutyl linker of the lead compound <b>1</b> were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC<sub>50</sub> inhibition in WNT/β<i>-</i>catenin signaling cellular reporter assay. The ","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2026-05-02T00:34:11.413Z","creation":"2022-02-09T13:21:01.669Z"},"accession":"S-EPMC8008393","cross_references":{"pubmed":["32511917"],"doi":["10.1021/acs.jmedchem.0c00208"]}}