Linzagolix

Summary

Linzagolix (CHEMBL3668014) is an approved small molecule (ATC H01CC04) targeting GNRHR; indicated across 6 conditions including endometriosis and uterine corpus leiomyoma.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: H01CC04
• Targets: 1 (GNRHR)
• Indications: 6 conditions
• Clinical trials: 17
• Chemistry: 508.4 Da · C22H15F3N2O7S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3668014
Name	Linzagolix
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	16656889
ATC	H01CC04
Molecular formula	C22H15F3N2O7S
Molecular weight	508.4
InChIKey	BMAAMIIYNNPHAB-UHFFFAOYSA-N

SMILES: COC1=C(C(=C(C=C1)F)F)COC2=C(C=C(C(=C2)N3C(=O)C4=C(SC=C4NC3=O)C(=O)O)F)OC

IUPAC name: 3-[5-[(2,3-difluoro-6-methoxyphenyl)methoxy]-2-fluoro-4-methoxyphenyl]-2,4-dioxo-1H-thieno[3,4-d]pyrimidine-5-carboxylic acid

Also known as: Klh-2109, KLH-2109, Linzagolix, OBE-2109, OBE2109, LINZAGOLIX, US9040693, 233

Parent form; salt/anhydrous children: CHEMBL4298171

Patent coverage: 95 distinct patent families (222 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 162 (73%) of the total. 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
GNRHR	GnRH1 receptor	Antagonist	7.44	0.1%	P30968

Broader ChEMBL bioactivity targets: 1 (assay-derived). Sample: Gonadotropin-releasing hormone receptor.

Bioactivity

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

Target	pChembl	Type	Value	Unit	Activity ID
GNRHR	7.82	IC50	15	nM	CHEMBL_ACT_17684367

Target pathways

Aggregated over 1 target gene(s): GNRHR.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Hormone ligand-binding receptors	1	GNRHR
G alpha (q) signalling events	1	GNRHR

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	1
gonadotropin secretion	1
cellular response to hormone stimulus	1
signal transduction	1
cellular response to gonadotropin-releasing hormone	1

Indications & clinical

Indications

6 indications (0 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
endometriosis	3	MONDO:0005133	EFO:0001065
uterine corpus leiomyoma	3	MONDO:0007886	EFO:0000731
leiomyoma	3	MONDO:0001572	HP:0000131
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: 17.

Phase distribution

Phase	Trials
PHASE3	10
PHASE2	5
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07015268	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of KLH-2109 in Patients With Endometriosis
NCT07378098	PHASE3	RECRUITING	to Evaluate the Efficacy and Safety of KLH-2109 in Patients With Uterine Fibroids and Menorrhagia
NCT03070899	PHASE3	COMPLETED	Efficacy and Safety of OBE2109 in Subjects With Heavy Menstrual Bleeding Associated With Uterine Fibroids
NCT03070951	PHASE3	COMPLETED	Efficacy and Safety of OBE2109 in Subjects With Heavy Menstrual Bleeding Associated With Uterine Fibroids
NCT03986944	PHASE3	TERMINATED	A Phase 3 Study to Confirm the Efficacy and Safety of Linzagolix to Treat Endometriosis-associated Pain
NCT03992846	PHASE3	COMPLETED	Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain.
NCT04335591	PHASE3	COMPLETED	Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain (EDELWEISS 6)
NCT04372121	PHASE3	TERMINATED	Extension to Study on Efficacy and Safety of Linzagolix for the Treatment of Endometriosis-associated Pain
NCT05440383	PHASE3	COMPLETED	A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia
NCT05445167	PHASE3	COMPLETED	A Clinical Study of KLH-2109 in Uterine Fibroids Patient With Menorrhagia and Pain
NCT01395940	PHASE2	COMPLETED	A Randomized Open Label Study of KLH-2109 in Patients With Endometriosis(1)
NCT01533532	PHASE2	COMPLETED	A Randomized, Placebo-controlled, Double-blind Study of KLH-2109 in Patients With Endometriosis (2)
NCT01629420	PHASE2	COMPLETED	A Phase II Randomized Open Label Study of KLH-2109 in Patients With Endometriosis
NCT02778399	PHASE2	COMPLETED	A Study to Assess the Efficacy and Safety of OBE2109 in Subjects With Endometriosis
NCT02778919	PHASE2	COMPLETED	Late Phase II Clinical Study of KLH-2109 in Patients With Endometriosis
NCT03961932	PHASE1	COMPLETED	Safety and Pharmacokinetics of Linzagolix in Female Subjects With Normal and Impaired Renal Function
NCT03962049	PHASE1	COMPLETED	Safety and Pharmacokinetics Study of Linzagolix in Female Subjects With Normal and Impaired Hepatic Function

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

13 molecules share ≥1 primary target. Top 13 by shared-target count:

Molecule	Source	Status	Shared targets
CETRORELIX	ChEMBL + PubChem	Phase 4 (approved)	GNRHR
DEGARELIX	ChEMBL + PubChem	Phase 4 (approved)	GNRHR
ELAGOLIX	ChEMBL + PubChem	Phase 4 (approved)	GNRHR
GANIRELIX	ChEMBL + PubChem	Phase 4 (approved)	GNRHR
RELUGOLIX	ChEMBL + PubChem	Phase 4 (approved)	GNRHR
ABARELIX	ChEMBL	Phase 4 (approved)	GNRHR
GONADORELIN	ChEMBL	Phase 4 (approved)	GNRHR
LEUPROLIDE	ChEMBL	Phase 4 (approved)	GNRHR
ACYLINE	ChEMBL	Phase 2	GNRHR
SUFUGOLIX	ChEMBL	Phase 2	GNRHR
Belzutifan	PubChem	Approved	GNRHR
Deslorelin	PubChem	Approved	GNRHR
Triptorelin	PubChem	Approved	GNRHR