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• W1995308188 abstract "Abstract Currently available progesterone (P4) receptor (PR) antagonists, such as mifepristone (RU486), lack specificity and display partial agonist properties, leading to potential drawbacks in their clinical use. Recent x-ray crystallographic studies have identified key contacts involved in the binding of agonists and antagonists with PR opening the way for a new rational strategy for inactivating PR. We report here the synthesis and characterization of a novel class of PR antagonists (APRn) designed from such studies. The lead molecule, the homosteroid APR19, displays in vivo endometrial anti-P4 activity. APR19 inhibits P4-induced PR recruitment and transactivation from synthetic and endogenous gene promoters. Importantly, it exhibits high PR selectivity with respect to other steroid hormone receptors and is devoid of any partial agonist activity on PR target gene transcription. Two-hybrid and immunostaining experiments reveal that APR19-bound PR is unable to interact with either steroid receptor coactivators 1 and 2 (SRC1 and SCR2) or nuclear receptor corepressor (NcoR) and silencing mediator of retinoid acid and thyroid hormone receptor (SMRT), in contrast to RU486-PR complexes. APR19 also inhibits agonist-induced phosphorylation of serine 294 regulating PR transcriptional activity and turnover kinetics. In silico docking studies based on the crystal structure of the PR ligand-binding domain show that, in contrast to P4, APR19 does not establish stabilizing hydrogen bonds with the ligand-binding cavity, resulting in an unstable ligand-receptor complex. Altogether, these properties highly distinguish APR19 from RU486 and likely its derivatives, suggesting that it belongs to a new class of pure antiprogestins that inactivate PR by a passive mechanism. These specific PR antagonists open new perspectives for long-term hormonal therapy." @default.
• W1995308188 created "2016-06-24" @default.
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• W1995308188 date "2013-06-01" @default.
• W1995308188 modified "2023-10-18" @default.
• W1995308188 title "A New Strategy for Selective Targeting of Progesterone Receptor With Passive Antagonists" @default.
• W1995308188 cites W1484666375 @default.
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• W1995308188 cites W1588517436 @default.
• W1995308188 cites W1593442063 @default.
• W1995308188 cites W1749258448 @default.
• W1995308188 cites W1907321242 @default.
• W1995308188 cites W1971746926 @default.
• W1995308188 cites W1971949613 @default.
• W1995308188 cites W1972848037 @default.
• W1995308188 cites W1974171707 @default.
• W1995308188 cites W1979136542 @default.
• W1995308188 cites W1984433201 @default.
• W1995308188 cites W1984751527 @default.
• W1995308188 cites W1986914259 @default.
• W1995308188 cites W1989150626 @default.
• W1995308188 cites W1992927495 @default.
• W1995308188 cites W1993482635 @default.
• W1995308188 cites W1996061414 @default.
• W1995308188 cites W2000011119 @default.
• W1995308188 cites W2000777228 @default.
• W1995308188 cites W2004857981 @default.
• W1995308188 cites W2007624933 @default.
• W1995308188 cites W2008539728 @default.
• W1995308188 cites W2014232493 @default.
• W1995308188 cites W2016921243 @default.
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• W1995308188 cites W2023307129 @default.
• W1995308188 cites W2023398724 @default.
• W1995308188 cites W2026370277 @default.
• W1995308188 cites W2026731274 @default.
• W1995308188 cites W2037043326 @default.
• W1995308188 cites W2048957217 @default.
• W1995308188 cites W2059329687 @default.
• W1995308188 cites W2063169494 @default.
• W1995308188 cites W2065958815 @default.
• W1995308188 cites W2067291023 @default.
• W1995308188 cites W2070327310 @default.
• W1995308188 cites W2074624944 @default.
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• W1995308188 cites W2085448623 @default.
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• W1995308188 cites W2131290017 @default.
• W1995308188 cites W2133270411 @default.
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• W1995308188 cites W2148131050 @default.
• W1995308188 cites W2151922331 @default.
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• W1995308188 doi "https://doi.org/10.1210/me.2012-1328" @default.
• W1995308188 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5415273" @default.
• W1995308188 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23579486" @default.
• W1995308188 hasPublicationYear "2013" @default.
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