Products/Services Used | Details | Operation |
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Mutagenesis Services> | .... by GenScript. Based on ERα LBD x- ray crystal structures, Q5 site-directed mutagenesis (New England Biolabs.... (residues 300-550) was synthesized by GenScript containing C381S, C417S, C530S, and L536S mutations in pET21 | Get A Quote |
Complex tissue-specific and cell-specific signaling by the estrogen receptor (ER) frequently leads to the development of resistance to endocrine therapy for breast cancer. Pure ER antagonists, which completely lack tissue-specific agonist activity, hold promise for preventing and treating endocrine resistance, however an absence of structural information hinders the development of novel candidates. Here we synthesize a small panel of benzopyrans with variable side chains to identify pure antiestrogens in a uterotrophic assay. We identify OP-1074 as a pure antiestrogen and a selective ER degrader (PA-SERD) that is efficacious in shrinking tumors in a tamoxifen-resistant xenograft model. Biochemical and cry... More