AZD9567   Click here for help

GtoPdb Ligand ID: 9812

Synonyms: AZD 9567 | AZD-9567 | compound 15 [PMID: 29424542] | example 1 [WO2016046260A1] [2]
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: AZD9567 is a synthetic, selective glucocorticoid receptor (GR) partial agonist [1]. It was designed to offer an improved side-effect profile compared to conventional full agonist GR anti-inflammatory dugs. AZD9567 is one of the chemical structures claimed in patent WO2016046260A1 [2].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 77.63
Molecular weight 494.21
XLogP 5.94
No. Lipinski's rules broken 1
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Canonical SMILES CC(C(C(c1ccccc1)Oc1ccc2c(c1)cnn2c1ccc(=O)n(c1)C)NC(=O)C(F)(F)C)C
Isomeric SMILES CC([C@@H]([C@@H](c1ccccc1)Oc1ccc2c(c1)cnn2c1ccc(=O)n(c1)C)NC(=O)C(F)(F)C)C
InChI InChI=1S/C27H28F2N4O3/c1-17(2)24(31-26(35)27(3,28)29)25(18-8-6-5-7-9-18)36-21-11-12-22-19(14-21)15-30-33(22)20-10-13-23(34)32(4)16-20/h5-17,24-25H,1-4H3,(H,31,35)/t24-,25+/m0/s1
Bioactivity Comments
In a cellular transactivation (TA) assay AZD9567 exhibits partial agonism (EC50 11nM, with agonist efficacy of 36%), and in the TA antagonist assay it has an IC50 of 160nM (antagonist efficacy of 56%) [1]. AZD9567 is highly selective for GR compared to the progesterone, mineralocorticoid, androgen and estrogen (α and β) receptors, as well as vs. a number of other proteins tested. Although AZD9567 is a partial agonist in transactivation assays, it mediates full GR translocation into the nucleus. Orally AZD9567 elicits potent anti-inflammatory effects in rat model of joint inflammation [1].
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
Glucocorticoid receptor Primary target of this compound Hs Agonist Partial agonist 8.0 pEC50 - 1
pEC50 8.0 (EC50 1.1x10-8 M) [1]
Description: In a cellular transactivation assay.
Glucocorticoid receptor Primary target of this compound Hs Agonist Partial agonist 8.4 pIC50 - 1
pIC50 8.4 (IC50 3.8x10-9 M) [1]
Description: Binding to human GR in vitro .
Progesterone receptor Hs Agonist Agonist 5.3 pIC50 - 1
pIC50 5.3 (IC50 5.3x10-6 M) [1]
Mineralocorticoid receptor Hs Agonist Agonist <4.4 pIC50 - 1
pIC50 <4.4 (IC50 >3.8x10-5 M) [1]