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Structure-Activity Relationships

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Estrogens and Antiestrogens I

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 135 / 1))

Abstract

Estrogens and antiestrogens are understood to exert their hormonal action after binding to the estrogen receptor (ER), a member of the nuclear receptor superfamily. Until recently, the knowledge of the shape of the full-length ER and the structure of the hormone-binding domain has been rather vague, due to the lack of cristallographie data. Information on the binding mode has been obtained from the three-dimensional structure of various ligands (WWiese and Brooks 1994). In October 1997, Brzozowski et al. (1997) published the crystal structures of the ligand-binding domain of the human ER (residues Ser 301 to Thr 553) in complex with the endogenous ligand 17β-estradiol and raloxifene as representative for a non-steroidal antagonist. Agonist and antagonist bind at the same site within the core of the ligand-binding domain, but demonstrate different binding modes, which induce distinct conformations in the transactivating domain 2. These structural data provide an ideal basis for the elucidation of the mode of action of antiestrogens and the rational design of new ligands.

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Authors
  1. E. von Angerer
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  1. Leiter Forschung und Entwicklung Jenapharm GmbH & Co. KG, Otto-Schott-Str. 15, D-07745, Jena, Germany

    Michael Oettel

  2. Leiter Forschung, Fertilitätskontrolle und Hormontherapie, Schering Aktiengesellschaft, D-13342, Berlin, Germany

    Ekkehard Schillinger

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© 1999 Springer-Verlag Berlin Heidelberg

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von Angerer, E. (1999). Structure-Activity Relationships. In: Oettel, M., Schillinger, E. (eds) Estrogens and Antiestrogens I. Handbook of Experimental Pharmacology, vol 135 / 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58616-3_5

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  • DOI: https://doi.org/10.1007/978-3-642-58616-3_5

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