fezolinetant   Click here for help

GtoPdb Ligand ID: 10422

Synonyms: compound 3 [PMID:26191358] | ESN-364 | ESN364 | Veoza® | Veozah® | Vezoa®
Approved drug
fezolinetant is an approved drug (FDA, EMA & UK MHRA (2023))
Compound class: Synthetic organic
Comment: Fezolinetant (ESN364) is a potent and selective neurokinin (NK) receptor 3 antagonist [3]. It was developed by Astellas Pharma as a non-hormonal therapeutic option for the treatment of female sex-hormone disorders such as polycystic ovary syndrome [2] and uterine fibroids, and for the management of the vasomotor symptoms (VMS) that drive menopausal hot flashes/flushes and/or night sweats [1,8-9].
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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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View interactive charts of activity data across species

fezolinetant is commercially available from our sponsors

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 6
Hydrogen bond donors 0
Rotatable bonds 3
Topological polar surface area 105.04
Molecular weight 358.1
XLogP 4.12
No. Lipinski's rules broken 0

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 Fc1ccc(cc1)C(=O)N1CCn2c(C1C)nnc2c1snc(n1)C
Isomeric SMILES Fc1ccc(cc1)C(=O)N1CCn2c([C@H]1C)nnc2c1snc(n1)C
InChI InChI=1S/C16H15FN6OS/c1-9-13-19-20-14(15-18-10(2)21-25-15)23(13)8-7-22(9)16(24)11-3-5-12(17)6-4-11/h3-6,9H,7-8H2,1-2H3/t9-/m1/s1
InChI Key PPSNFPASKFYPMN-SECBINFHSA-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/)
No information available.
Summary of Clinical Use Click here for help
Fezolinetant was progressed to Phase 3 clinical evaluation as a non-hormonal therapy for vasomotor symptoms (VMS) due to menopause. Click here to link to ClinicalTrials.gov's full list of fezolinetant studies. The FDA granted clinical approval as a treatment for moderate to severe VMS in May 2023 [6,9].
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT05033886 A Study of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause Phase 3 Interventional Astellas Pharma Inc
NCT05034042 A Study to Find the Best Dose of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause Phase 2 Interventional Astellas Pharma Inc
NCT03192176 A Dose-ranging Study of the Efficacy of ESN364 in Postmenopausal Women Suffering Vasomotor Symptoms (Hot Flashes) Phase 2 Interventional Astellas Pharma Inc In this study fezolinetant was well-tolerated. It rapidly reduced moderate/severe menopausal vasomotor symptoms.
NCT04003155 A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause Phase 3 Interventional Astellas Pharma Inc The SKYLIGHT 1 study. 5,10
NCT04003389 A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause Phase 3 Interventional Astellas Pharma Inc The SKYLIGHT 4 study. 7
NCT04003142 A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause - 2 Phase 3 Interventional Astellas Pharma Inc The SKYLIGHT 2 study. 4,10
Pharmacokinetics Click here for help
Biotransformation/Metabolism
Primarily metabolised by CYP1A2, with some metabolism by CYP2C9 and CYP2C19. Concomitant use of moderate or strong CYP1A2 inhibitors (e.g. fluvoxamine, mexiletine, enoxacin) with fezolinetant is known to increase the drug's plasma Cmax, and is contraindicated.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)