amcenestrant   Click here for help

GtoPdb Ligand ID: 10566

Synonyms: compound 43d [PMID: 31721572] | SAR-439859 | SAR439859
PDB Ligand
Compound class: Synthetic organic
Comment: Amcenestrant (SAR439859) is a selective estrogen receptor degrader (SERD) [1]. It was designed (by Sanofi) to have improved pharmacokinetic properties compared to the existing clinically used SERD, fulvestrant. An X-ray structure of SAR439859 in complex with the ERα ligand binding domain indicates that the ligand occupies the orthosteric estradiol binding cavity.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 49.77
Molecular weight 553.16
XLogP 8.95
No. Lipinski's rules broken 1
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Canonical SMILES FCCCN1CCC(C1)Oc1ccc(cc1)C1=C(CCCc2c1ccc(c2)C(=O)O)c1ccc(cc1Cl)Cl
Isomeric SMILES FCCCN1CCC(C1)Oc1ccc(cc1)C1=C(CCCc2c1ccc(c2)C(=O)O)c1ccc(cc1Cl)Cl
InChI InChI=1S/C31H30Cl2FNO3/c32-23-8-12-27(29(33)18-23)28-4-1-3-21-17-22(31(36)37)7-11-26(21)30(28)20-5-9-24(10-6-20)38-25-13-16-35(19-25)15-2-14-34/h5-12,17-18,25H,1-4,13-16,19H2,(H,36,37)
Bioactivity Comments
SAR439859 degrades ERα in MCF-7 cells (by fluorescence detection following 4h treatment) with an EC50 of 0.2 nM, and an efficacy of 98% compared to fulvestrant control [1]. Orally dosed SAR439859 exhibits anti-tumour activity in xenograft murine models of ER+ve breast cancer, and is well tolerated. Direct agonist/antagonist activity of SAR439859 at the ERα is not reported in the discovery article.
Selectivity at nuclear hormone receptors
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Estrogen receptor-α Hs Antagonist Antagonist - - - 1
Description: Functional antagonist of ERα activity by promoting receptor degradation.