{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu J"],"funding":["Louisiana Cancer Research Consortium","NIMHD NIH HHS","National Institute on Minority Health and Health Disparities"],"pagination":["102-106"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5238461"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(1)"],"pubmed_abstract":["Development of orally bioavailable nonsteroidal selective estrogen receptor downregulators (SERDs) provides clinical opportunities for the long-term treatment and adjuvant therapy of breast cancer at all stages. We describe the design, synthesis, and identification of a boron-modified GW7604 derivative (GLL398, <b>9</b>), a SERD candidate, in which a boronic acid functional group replaces the phenolic hydroxyl group of GW7604. Compound <b>9</b> strongly binds to ERα in a fluorescence resonance energy transfer binding assay (IC<sub>50</sub> = 1.14 nM) and potently degrades ERα in MCF-7 breast cancer cells (IC<sub>50</sub> = 0.21 μM). Most importantly, the introduction of the boronic acid group confers superior oral bioavailability of <b>9</b> (AUC = 36.9 μg·h/mL) in rats as compared to GW76"],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Rational Design of a Boron-Modified Triphenylethylene (GLL398) as an Oral Selective Estrogen Receptor Downregulator."],"pmcid":["PMC5238461"],"funding_grant_id":["2G12MD007595","G12 MD007595"],"pubmed_authors":["Ma P","Liu J","Zhong Q","Zheng S","Wang G","Guo S","Bratton MR","Zhang C","Wiese TE","Zhang Q","Skripnikova EV"],"additional_accession":[]},"is_claimable":false,"name":"Rational Design of a Boron-Modified Triphenylethylene (GLL398) as an Oral Selective Estrogen Receptor Downregulator.","description":"Development of orally bioavailable nonsteroidal selective estrogen receptor downregulators (SERDs) provides clinical opportunities for the long-term treatment and adjuvant therapy of breast cancer at all stages. We describe the design, synthesis, and identification of a boron-modified GW7604 derivative (GLL398, <b>9</b>), a SERD candidate, in which a boronic acid functional group replaces the phenolic hydroxyl group of GW7604. Compound <b>9</b> strongly binds to ERα in a fluorescence resonance energy transfer binding assay (IC<sub>50</sub> = 1.14 nM) and potently degrades ERα in MCF-7 breast cancer cells (IC<sub>50</sub> = 0.21 μM). Most importantly, the introduction of the boronic acid group confers superior oral bioavailability of <b>9</b> (AUC = 36.9 μg·h/mL) in rats as compared to GW76","dates":{"release":"2017-01-01T00:00:00Z","publication":"2017 Jan","modification":"2025-04-04T09:03:15.616Z","creation":"2019-03-27T02:34:11Z"},"accession":"S-EPMC5238461","cross_references":{"pubmed":["28105283"],"doi":["10.1021/acsmedchemlett.6b00410"]}}