Relugolix is a non-peptide, orally active gonadotropin-releasing hormone (GnRH) antagonist with IC50 of 0.33 nM in the presence of 40% fetal bovine serum. It possesses higher affinity and potent antagonistic activity compared with TAK-013.
Gonadotropin-releasing hormone (GnRH) is a decapeptide, which is synthesized in the hypothalamus and plays a pivotal role in the secretion of gonadotropins, such as luteinizing hormone and follicle-stimulating hormone. Relugolix is a novel, non-peptide, orally active GnRH antagonist with IC50s of 0.33 and 0.32 nM for human and monkey GnRH receptor, respectively. In vivo, twice-daily oral administration of relugolix (10 mg/kg) for 4 weeks reduced the prostate weight to castrate levels in male knock-in mice. In female knock-in mice, twice-daily oral administration of relugolix (100 mg/kg) induced constant diestrous phases within the first week, decreased the uterus weight to ovariectomized levels and downregulated GnRH receptor mRNA in the pituitary after 4 weeks. Moreover, gonadal function of relugolix-treated knock-in mice began to recover after 5 days and almost completely recovered within 14 days after drug withdrawal in both sexes suggesting suppression the hypothalamic-pituitary-gonadal axis caused by relugolix is reversible[3].
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