Sufugolix (
INNTooltip International Nonproprietary Name,
BANTooltip British Approved Name) (developmental code name TAK-013) is a
non-peptide,
orally-active,
selectiveantagonist of the
gonadotropin-releasing hormone receptor (GnRHR) (
IC50Tooltip Half-maximal inhibitory concentration = 0.1 and 0.06 nM for
affinity and in vitroinhibition, respectively).[1] It was under development by
Takeda for the treatment of
endometriosis and
uterine leiomyoma and reached
phase IIclinical 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 P450inhibition and improved in vivo GnRHR antagonistic activity) in comparison.[4]
^
abcSasaki S, Cho N, Nara Y, Harada M, Endo S, Suzuki N, et al. (January 2003). "Discovery of a thieno[2,3-d]pyrimidine-2,4-dione bearing a p-methoxyureidophenyl moiety at the 6-position: a highly potent and orally bioavailable non-peptide antagonist for the human luteinizing hormone-releasing hormone receptor". Journal of Medicinal Chemistry. 46 (1): 113–124.
doi:
10.1021/jm020180i.
PMID12502365.
^Lanier MC, Feher M, Ashweek NJ, Loweth CJ, Rueter JK, Slee DH, et al. (August 2007). "Selection, synthesis, and structure-activity relationship of tetrahydropyrido[4,3-d]pyrimidine-2,4-diones as human GnRH receptor antagonists". Bioorganic & Medicinal Chemistry. 15 (16): 5590–5603.
doi:
10.1016/j.bmc.2007.05.029.
PMID17561404.
^Miwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M, et al. (July 2011). "Discovery of 1-{4-[1-(2,6-difluorobenzyl)-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea (TAK-385) as a potent, orally active, non-peptide antagonist of the human gonadotropin-releasing hormone receptor". Journal of Medicinal Chemistry. 54 (14): 4998–5012.
doi:
10.1021/jm200216q.
PMID21657270.
^Kohout TA, Xie Q, Reijmers S, Finn KJ, Guo Z, Zhu YF, Struthers RS (August 2007). "Trapping of a nonpeptide ligand by the extracellular domains of the gonadotropin-releasing hormone receptor results in insurmountable antagonism". Molecular Pharmacology. 72 (2): 238–247.
doi:
10.1124/mol.107.035535.
PMID17409285.
S2CID23980337.