Fezolinetant

Summary

Fezolinetant (CHEMBL3608680) is an approved small-molecule neurokinin-3 receptor antagonist (ATC G02CX06) targeting TACR3; indicated across 3 conditions including liver disorder and kidney disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G02CX06
• Targets: 1 (TACR3)
• Indications: 3 conditions
• Clinical trials: 27
• Chemistry: 358.4 Da · C16H15FN6OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3608680
Name	Fezolinetant
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	117604931
ChEBI	CHEBI:229236
ATC	G02CX06
Molecular formula	C16H15FN6OS
Molecular weight	358.4
InChIKey	PPSNFPASKFYPMN-SECBINFHSA-N

SMILES: C[C@@H]1C2=NN=C(N2CCN1C(=O)C3=CC=C(C=C3)F)C4=NC(=NS4)C

IUPAC name: (4-fluorophenyl)-[(8R)-8-methyl-3-(3-methyl-1,2,4-thiadiazol-5-yl)-6,8-dihydro-5H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]methanone

ChEBI definition: A triazolopyrazine that is 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine substituted by 3-methyl-1,2,4-thiadiazol-5-yl, 4-fluorobenzoyl and methyl groups at positions 3, 7, and 8R, respectively. It is a prescription medicine used to reduce moderate to severe vasomotor symptoms due to menopause.

Pharmacological roles (ChEBI): neurokinin-3 receptor antagonist.

Also known as: A-2693, A2693, ES-256364, ESN-364, Esn364, ESN364, Fezolinetant, Veoza, Veozah, FEZOLINETANT

Patent coverage: 47 distinct patent families (116 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
TACR3	NK3 receptor	Antagonist	7.6	0%	P29371

Broader ChEMBL bioactivity targets: 6 (assay-derived). Sample: Voltage-gated inwardly rectifying potassium channel KCNH2, Neuromedin-K receptor, Cytochrome P450 2C9, Cytochrome P450 3A4, Cytochrome P450 2C19, Neuromedin-K receptor.

Bioactivity

ChEMBL activities: 13 potent at pChembl ≥ 5 of 19 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TACR3	7.75	IC50	18	nM	CHEMBL_ACT_17786170
TACR3	7.75	IC50	18	nM	CHEMBL_ACT_26904711
TACR3	7.75	IC50	18	nM	CHEMBL_ACT_28186715
TACR3	7.7	IC50	19.95	nM	CHEMBL_ACT_15689410
TACR3	7.66	Ki	21.8	nM	CHEMBL_ACT_29231730
TACR3	7.64	Ki	23	nM	CHEMBL_ACT_17786217
TACR3	7.64	Ki	23	nM	CHEMBL_ACT_26904714
TACR3	7.64	Ki	23	nM	CHEMBL_ACT_27653798
TACR3	7.64	Ki	23	nM	CHEMBL_ACT_28186718
TACR3	7.6	Ki	25.12	nM	CHEMBL_ACT_15689424
TACR3	6.96	IC50	109.8	nM	CHEMBL_ACT_26136166
P16177	6.66	Ki	219	nM	CHEMBL_ACT_15689917
TACR3	6.3	IC50	500.8	nM	CHEMBL_ACT_26136209

Target pathways

Aggregated over 1 target gene(s): TACR3.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Tachykinin receptors bind tachykinins	1	TACR3
G alpha (q) signalling events	1	TACR3

Dominant GO biological processes

GO term	Targets
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
phospholipase C-activating tachykinin receptor signaling pathway	1
tachykinin receptor signaling pathway	1
positive regulation of heart rate	1
response to estradiol	1
positive regulation of luteinizing hormone secretion	1
regulation of dopamine metabolic process	1
response to cocaine	1
drinking behavior	1
positive regulation of blood pressure	1
vagina development	1
regulation of feeding behavior	1
positive regulation of uterine smooth muscle contraction	1
positive regulation of flagellated sperm motility	1
conditioned place preference	1

Indications & clinical

Indications

3 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	EFO:0003086

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 27.

Phase distribution

Phase	Trials
PHASE3	10
PHASE2	8
PHASE1	5
Not specified	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06440967	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy
NCT06975111	PHASE2/PHASE3	RECRUITING	Focusing on the Menopausal Transition to Improve Mid-Life Women’s Health
NCT07606664	PHASE3	NOT_YET_RECRUITING	Fezolinetant and Vascular Health and Brain Health
NCT04003142	PHASE3	COMPLETED	A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause - 2
NCT04003155	PHASE3	COMPLETED	A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women Going Through Menopause
NCT04003389	PHASE3	COMPLETED	A Study to Find Out How Safe Long-term Treatment With Fezolinetant is in Women With Hot Flashes Going Through Menopause
NCT04234204	PHASE3	COMPLETED	A Study to Find Out if Fezolinetant Helps Reduce Moderate to Severe Hot Flashes in Women in Asia Going Through Menopause
NCT04451226	PHASE3	COMPLETED	A Study to Assess the Safety and Tolerability of Fezolinetant in Women Seeking Treatment for Relief of Vasomotor Symptoms (VMS) Associated With Menopause
NCT05033886	PHASE3	COMPLETED	A Study of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause
NCT06206408	PHASE3	COMPLETED	A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Japanese Women Going Through Menopause
NCT06206421	PHASE3	COMPLETED	A Study to Assess Long-term Safety of Fezolinetant Given to Japanese Women Going Through Menopause
NCT06917313	PHASE2	RECRUITING	FLASH-Breast: Evaluating the Efficacy of Fezolinetant in Reducing Vasomotor Symptoms in Women With Breast Cancer on Endocrine Therapy
NCT06972875	PHASE2	RECRUITING	Fezolinetant for Treating Hot Flashes in Men With Prostate Cancer
NCT07568236	PHASE2	NOT_YET_RECRUITING	A Trial on Fezolinetant for Vasomotor Symptoms in Men Receiving Androgen Deprivation Therapy (ADT)
NCT03192176	PHASE2	COMPLETED	A Dose-ranging Study of the Efficacy of ESN364 in Postmenopausal Women Suffering Vasomotor Symptoms (Hot Flashes)
NCT05034042	PHASE2	COMPLETED	A Study to Find the Best Dose of Fezolinetant to Treat Hot Flashes in Women Going Through Menopause
NCT05419908	PHASE2	COMPLETED	Trial to Investigate the Effect of ESN364 in Early Postmenopausal Women Suffering From Hot Flashes
NCT06617455	PHASE2	TERMINATED	Fezolinetant for the Improvement of Vasomotor Symptoms in Breast Cancer Patients Taking Endocrine Therapy, VENT Trial
NCT06812754	PHASE2	COMPLETED	A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Chinese Women Going Through Menopause
NCT03436849	PHASE1	COMPLETED	A Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ESN364 in Healthy Japanese Male and Pre- and Post-menopausal Female Subjects
NCT04476849	PHASE1	COMPLETED	A Study to Investigate the Effect of Renal Impairment on the Safety and Tolerability of Fezolinetant Compared to Participants With Normal Renal Function
NCT04482270	PHASE1	COMPLETED	A Study to Investigate the Effect of Mild and Moderate Hepatic Impairment on the Safety and Tolerability of Fezolinetant Compared to Participants With Normal Hepatic Function
NCT04641260	PHASE1	COMPLETED	A Study to Assess the Effect of Food With Fezolinetant in Healthy Female Participants
NCT04793204	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics and Safety of Fezolinetant in Healthy Chinese Female Subjects
NCT06049797	Not specified	ACTIVE_NOT_RECRUITING	A Study Following Women in Menopause Treated With a Non-hormonal Therapy for Hot Flashes and Night Sweats
NCT07455812	Not specified	ACTIVE_NOT_RECRUITING	A Study in Germany to Learn About the Value of Fezolinetant in Treating Hot Flashes and Night Sweats in Women During Menopause
NCT07602530	Not specified	RECRUITING	A Study in Canada to Follow Outcomes of Women in Menopause Treated With Fezolinetant for Hot Flashes, When Given in Clinical Practice

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

Molecule	Source	Status	Shared targets
APREPITANT	ChEMBL + PubChem	Phase 4 (approved)	TACR3
SERLOPITANT	ChEMBL	Phase 3	TACR3
AZD-7624	ChEMBL	Phase 2	TACR3
ELEDOISIN	ChEMBL	Phase 2	TACR3
OSANETANT	ChEMBL	Phase 2	TACR3
PAVINETANT	ChEMBL	Phase 2	TACR3
TALNETANT	ChEMBL	Phase 2	TACR3
Belzutifan	PubChem	Approved	TACR3