Sufugolix

Sufugolix (INNTooltip International Nonproprietary Name, BANTooltip British Approved Name) (developmental code name TAK-013) is a non-peptide, orally-active, selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (IC₅₀Tooltip Half-maximal inhibitory concentration = 0.1 and 0.06 nM for affinity and in vitro inhibition, respectively).^[1] It was under development by Takeda for the treatment of endometriosis and uterine leiomyoma and reached phase II clinical trials for both of these indications, but was subsequently discontinued.^[2][3] It seems to have been supplanted by relugolix (TAK-385), which is also under development by Takeda for the treatment of these conditions and has a more favorable drug profile (including reduced cytochrome P450 inhibition and improved in vivo GnRHR antagonistic activity) in comparison.^[4]

Sufugolix

Clinical data
Other names	TAK-013
Routes of administration	By mouth
Drug class	GnRH modulator; GnRH antagonist; Antigonadotropin
ATC code	None
Identifiers
IUPAC name 1-[4-[5-[[benzyl(methyl)amino]methyl]-1-[(2,6-difluorophenyl)methyl]-2,4-dioxo-3-phenylthieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea
CAS Number	308831-61-0
PubChem CID	3038517
ChemSpider	2302081
UNII	56S17Z6X9M
CompTox Dashboard (EPA)	DTXSID40184893
Chemical and physical data
Formula	C36H31F2N5O4S
Molar mass	667.73 g·mol−1
3D model (JSmol)	Interactive image
SMILES CONC(=O)Nc1ccc(-c2sc3c(c2CN(C)Cc2ccccc2)c(=O)n(-c2ccccc2)c(=O)n3Cc2c(F)cccc2F)cc1
InChI InChI=1S/C36H31F2N5O4S/c1-41(20-23-10-5-3-6-11-23)21-28-31-33(44)43(26-12-7-4-8-13-26)36(46)42(22-27-29(37)14-9-15-30(27)38)34(31)48-32(28)24-16-18-25(19-17-24)39-35(45)40-47-2/h3-19H,20-22H2,1-2H3,(H2,39,40,45) Key:UCQSBGOFELXYIN-UHFFFAOYSA-N

Oral administration of sufugolix at a dose of 30 mg/kg to castrated male cynomolgus monkeys resulted in nearly complete suppression of luteinizing hormone levels.^[1] The duration of action was more than 24 hours, indicating a long elimination half-life of the drug.^[1] The suppressive effects of sufugolix on gonadotropin and sex hormone levels are rapidly reversible with discontinuation.^[5]

Unlike various other GnRHR antagonists, sufugolix has been elucidated to be a non-competitive or insurmountable/trapping antagonist of the GnRHR rather than a competitive antagonist.^[6][7]

See also

• Gonadotropin-releasing hormone receptor § Antagonists