Linzagolix

Linzagolix, sold under the brand name Yselty, is a medication used in the treatment of uterine fibroids and endometriosis.^[1][6][7] Linzagolix is a small-molecule, non-peptide, orally active gonadotropin-releasing hormone antagonist (GnRH antagonist) developed by Kissei Pharmaceutical and ObsEva.^[8][9][2]

Linzagolix

Clinical data
Pronunciation	/ˌlɪnzəˈɡoʊlɪks/ LINZ-ə-GOH-liks
Trade names	Yselty
Other names	KLH-2109; OBE-2109
Routes of administration	By mouth[1][2]
Drug class	GnRH modulator; GnRH antagonist; Antigonadotropin
ATC code	H01CC04 (WHO)
Legal status
Legal status	AU: S4 (Prescription only)[3] UK: POM (Prescription only)[4] EU: Rx-only[1][5]
Identifiers
IUPAC name 3-{5-[(2,3-difluoro-6-methoxyphenyl)methoxy]-2-fluoro-4-methoxyphenyl}-2,4-dioxo-1,2,3,4-tetrahydrothieno[3,4-d]pyrimidine-5-carboxylic acid
CAS Number	935283-04-8 as choline: 1321816-57-2
PubChem CID	16656889
ChemSpider	17590169
UNII	7CDW97HUEX
KEGG	D11608 as choline: D11609
ChEMBL	ChEMBL3668014 as choline: ChEMBL4298171
Chemical and physical data
Formula	C22H15F3N2O7S
Molar mass	508.42 g·mol−1
3D model (JSmol)	Interactive image
SMILES COc1cc(F)c(-n2c(=O)[nH]c3csc(C(=O)O)c3c2=O)cc1OCc1c(OC)ccc(F)c1F
InChI InChI=1S/C22H15F3N2O7S/c1-32-14-4-3-10(23)18(25)9(14)7-34-16-6-13(11(24)5-15(16)33-2)27-20(28)17-12(26-22(27)31)8-35-19(17)21(29)30/h3-6,8H,7H2,1-2H3,(H,26,31)(H,29,30) Key:BMAAMIIYNNPHAB-UHFFFAOYSA-N

In June 2022, it was approved for medical use in the European Union and in the United Kingdom.^[1][5][10]

Medical uses

Linzagolix is indicated for treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age and for treatment of intractable endometriosis.^[1][7]

Available forms

Linzagolix is available as linzagolix choline, the choline salt of linzagolix, in the form of 100 and 200 mg film-coated oral tablets.^[6]

Pharmacology

Pharmacodynamics

Linzagolix acts as a selective antagonist of the GnRH receptor, the biological target of GnRH.^[6] By blocking this receptor, linzagolix prevents GnRH-mediated secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and prevents them from signaling the gonads to produce sex hormones including estrogens, progesterone, and androgens.^[6][11]

In clinical studies, linzagolix fully suppressed estradiol levels (median <20 pg/mL) in women at a dosage of 200 mg/day, whereas partial suppression of estradiol levels (median 20–60 pg/mL) occurred at a dosage 100 mg/day.^[6] Progesterone levels were also variably suppressed with these dosages.^[6]

Pharmacokinetics

The elimination half-life of linzagolix with repeated administration is approximately 15 hours.^[6]

Society and culture

Legal status

On 16 December 2021, and on 22 April 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Yselty, intended for the treatment of symptoms of uterine fibroids.^[12] The applicant for this medicinal product is ObsEva Ireland Ltd.^[12] Linzagolix was approved for medical use in the European Union in June 2022.^[1][5]

Brand names

Linzagolix is sold under the brand name Yselty.^[6]

Availability

Linzagolix is available in the European Union and in the United Kingdom.^[6][10]