biostudies-literatureLiu JLouisiana Cancer Research ConsortiumNIMHD NIH HHSNational Institute on Minority Health and Health Disparities102-106https://www.ebi.ac.uk/biostudies/studies/S-EPMC5238461biostudies-literatureUnknown8(1)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 (IC₅₀ = 1.14 nM) and potently degrades ERα in MCF-7 breast cancer cells (IC₅₀ = 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 GW76ACS medicinal chemistry lettersRational Design of a Boron-Modified Triphenylethylene (GLL398) as an Oral Selective Estrogen Receptor Downregulator.PMC52384612G12MD007595G12 MD007595Ma PLiu JZhong QZheng SWang GGuo SBratton MRZhang CWiese TEZhang QSkripnikova EVfalseRational Design of a Boron-Modified Triphenylethylene (GLL398) as an Oral Selective Estrogen Receptor Downregulator.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 (IC₅₀ = 1.14 nM) and potently degrades ERα in MCF-7 breast cancer cells (IC₅₀ = 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 GW762017-01-01T00:00:00Z2017 Jan2025-04-04T09:03:15.616Z2019-03-27T02:34:11ZS-EPMC52384612810528310.1021/acsmedchemlett.6b00410