Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms.

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Geistlinger TR, McReynolds AC, Guy RK

Ligand-selective inhibition of the interaction of steroid receptor coactivators and estrogen receptor isoforms.

Chem Biol. 2004 Feb;11(2):273-81.

PubMed ID
15123288 [ View in PubMed
]
Abstract

Ligand-dependent nuclear hormone receptor (NR) signaling requires direct interaction between NR and the steroid receptor coactivators (SRC). Herein we utilize a library of SRC2 peptidomimetics to select for specific inhibitors of the interaction of SRC2 with the two estrogen receptor (ER) isoforms, ERalpha and ERbeta, in the presence of three different ligands: 17beta-estradiol, diethylstilbesterol, and genistein. The pattern of inhibitor selectivity for each ER isoform varied depending upon which ligand was present, thus demonstrating that the ligands exert unique allosteric effects upon the surface of the SRC binding pocket. Several of the lead compounds are highly (>100-fold) selective for blocking the binding of SRC2 to ERalpha, in preference to ERbeta, in the presence of one ligand and therefore may prove useful for decoupling ERbeta signaling from ERalpha signaling.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
DiethylstilbestrolEstrogen receptor betaProteinHumans
Yes
Agonist
Details
DiethylstilbestrolNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails
Estradiol acetateNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails
Estradiol benzoateNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails
Estradiol cypionateNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails
Estradiol dienanthateNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails
Estradiol valerateNuclear receptor coactivator 2ProteinHumans
Unknown
Not AvailableDetails