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'''Sufugolix''' ({{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|BAN|British Approved Name}}) (developmental code name '''TAK-013''') is a [[non-peptide]], [[Bioavailability#In pharmacology|orally]]-active, [[binding selectivity|selective]] [[gonadotropin-releasing hormone receptor antagonist|antagonist]] of the [[gonadotropin-releasing hormone receptor]] (GnRHR) ({{abbrlink|IC<sub>50</sub>|Half-maximal inhibitory concentration}} = 0.1 and 0.06 nM for [[affinity (pharmacology)|affinity]] and ''in vitro'' [[receptor antagonist|inhibition]], respectively).<ref name="pmid12502365">{{cite journal | vauthors = Sasaki S, Cho N, Nara Y, Harada M, Endo S, Suzuki N, Furuya S, Fujino M | title = 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 = J. Med. Chem. | volume = 46 | issue = 1 | pages = 113–24 | year = 2003 | pmid = 12502365 | doi = 10.1021/jm020180i
Oral administration of sufugolix at a dose of 30 mg/kg to [[castration|castrated]] male [[cynomolgus monkey]]s resulted in nearly complete suppression of [[luteinizing hormone]] levels.<ref name="pmid12502365" /> The [[duration of action]] was more than 24 hours, indicating a long [[elimination half-life]] of the drug.<ref name="pmid12502365" /> The suppressive effects of sufugolix on [[gonadotropin]] and [[sex hormone]] levels are rapidly reversible with discontinuation.<ref name="pmid12679460">{{cite journal | vauthors = Hara T, Araki H, Kusaka M, Harada M, Cho N, Suzuki N, Furuya S, Fujino M | title = Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys | journal = J. Clin. Endocrinol. Metab. | volume = 88 | issue = 4 | pages = 1697–704 | year = 2003 | pmid = 12679460 | doi = 10.1210/jc.2002-021065
Unlike various other GnRHR antagonists, sufugolix has been elucidated to be a [[non-competitive antagonist|non-competitive or insurmountable/trapping antagonist]] of the GnRHR rather than a [[competitive antagonist]].<ref name="pmid17409285">{{cite journal | vauthors = Kohout TA, Xie Q, Reijmers S, Finn KJ, Guo Z, Zhu YF, Struthers RS | title = Trapping of a nonpeptide ligand by the extracellular domains of the gonadotropin-releasing hormone receptor results in insurmountable antagonism | journal = Mol. Pharmacol. | volume = 72 | issue = 2 | pages = 238–47 | year = 2007 | pmid = 17409285 | doi = 10.1124/mol.107.035535 | s2cid = 23980337
==See also==
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