miricorilant   Click here for help

GtoPdb Ligand ID: 10059

Synonyms: C-118335 | C118335 | compound 7 [PMID: 23131342] | CORT118335
Compound class: Synthetic organic
Comment: Miricorilant (CORT118335) is a potent, orally active non-steroidal glucocorticoid receptor (GR) antagonist that is being developed by Corcept Therapeutics [2]. Selective GR antagonists are being investigated for their potential to mitigate antipsychotic-induced weight gain, a beneficial activity that was first identified using the dual GR/progesterone receptor antagonist mifepristone [1].
Hunt et al. (2010) specify CORT118335 with the InChIKey GVVUZBSCYAVFTI-IYARVYRRSA-N and as the trans isomer (or the (1r,4r) isomer) [2], which corresponds to the chemical structure submitted to the WHO for the INN miricorilant. Note that PubChem lists this compound in the form without any specified stereochemistry, with PubChem CID 66550324, and that ChEMBL record the cis (or (1s,4s)) isomer as CHEMBL2204043 (InChIKey GVVUZBSCYAVFTI-HDICACEKNA-N).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 2
Rotatable bonds 5
Topological polar surface area 65.72
Molecular weight 428.17
XLogP 6.11
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=c1[nH]c(=O)c(c([nH]1)C1CCC(CC1)c1ccccc1)Cc1cccc(c1)C(F)(F)F
Isomeric SMILES O=c1[nH]c(=O)c(c([nH]1)[C@@H]1CC[C@H](CC1)c1ccccc1)Cc1cccc(c1)C(F)(F)F
InChI InChI=1S/C24H23F3N2O2/c25-24(26,27)19-8-4-5-15(13-19)14-20-21(28-23(31)29-22(20)30)18-11-9-17(10-12-18)16-6-2-1-3-7-16/h1-8,13,17-18H,9-12,14H2,(H2,28,29,30,31)/t17-,18-
InChI Key GVVUZBSCYAVFTI-IYARVYRRSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
Bioactivity Comments
In a reporter gene assay (measured as inhibition of dexamethasone induced luciferase expression through the glucocorticoid response element) CORT118335 has a Ki of 24 nM [2]. CORT118335 exhibited good selectivity against PR, ER and AR, with no significant affinity in receptor binding assays, and in reporter gene assays in comparison to GR only selectivity against MR (8-fold) was noteworthy. CORT118335 did not exhibit any significant liability in terms of inhibition of any of the five major human cytochrome p450 enzymes (3A4, 2D6, 1A2, 2C9, 2C19). Preclinical studies show that CORT118335 is efficacious in the rat olanzapine-induced weight gain model.
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 Antagonist Antagonist 8.1 pKi - 2
⤷ pKi 8.1 (Ki 8x10-9 M) [2]
Description: Determined by measuring displacement of [3H]dexamethasone from recombinant baculovirus derived human GR.