9B2B

Estrogen Receptor Alpha Ligand Binding Domain in Complex with a Complete Estrogen Receptor Antagonists that Favors Tetramer Formation

This is a non-PDB format compatible entry.

Summary for 9B2B

• Entry DOI: 10.2210/pdb9b2b/pdb
• Descriptor: Estrogen receptor, 2-chloro-3-{[{[1-(2-fluorophenyl)cyclopentyl]methyl}(4-{[1-(3-fluoropropyl)azetidin-3-yl]oxy}phenyl)amino]methyl}phenol (3 entities in total)
• Functional Keywords: estrogen receptor, antiestrogen, alpha helical bundle, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 118296.36

Authors

Fink, E.C.,Chawla, R.,Wells, K.S.,Barratt, S.,Myles, D.C.,Pena, G.,Robello, B.W.,Ng, R.,Fanning, S.W. (deposition date: 2024-03-14, release date: 2025-08-27, Last modification date: 2026-09-09)

Primary citation

Fink, E.C.,Chawla, R.,Hancock, G.R.,Wells, K.S.,Barratt, S.,Myles, D.C.,Pena, G.,Robello, B.W.,Hearn, B.R.,Fanning, S.W.
Allosteric Induction of Estrogen Receptor Ligand Binding Domain Tetramerization by a Distinct Complete Estrogen Receptor Antagonist.
Acs Med.Chem.Lett., 17:441-449, 2026

PubMed Abstract: Complete estrogen receptor antagonists (CERANs) are effective against advanced estrogen receptor-positive (ER+) breast cancers, but current chemical scaffolds limit our ability to explore the full range of ER pharmacology. We report the synthesis of OP-1690 (), a CERAN featuring a distinct unconstrained core. Structural and biophysical studies reveal that uniquely promotes estrogen receptor alpha (ERα) ligand binding domain (LBD) tetramer formation, which goes beyond the conventional homodimer. This study shows how new CERAN scaffolds can reveal unrecognized mechanisms of action.

PubMed: 41704390
DOI: 10.1021/acsmedchemlett.5c00667

Experimental method

X-RAY DIFFRACTION (2.08 Å)