Relugolix

Relugolix (TAK-385)?is a potent, orally active, nonpeptidic gonadotropin-releasing hormone (GnRH) antagonist. Relugolix possesses high affinity and potent antagonistic activity for human receptor (binding IC₅₀=0.33 nM) and monkey receptor (IC₅₀=0.32 nM) compared with TAK-013 (HY-100209)^[1]. Relugolix is used for the study of sex-hormone-dependent diseases, such as including endometriosis, uterine fibroids and prostate cancer et al^[2]. IC50 & Target: IC50: 0.33 nM (human GnRH)
IC50: 0.32 nM (monkey GnRH)^[2] In Vitro: Relugolix exhibits strong binding affinity (IC₅₀=0.32 nM) for the monkey receptor comparable to that for the human receptor (IC₅₀=0.33 nM) while displaying a 30000-fold decrease for the rat receptor (IC₅₀=9800 nM). The antagonistic in vitro activity of TAK-385 with respect to the human receptor (IC₉₀=18 nM) exceeded that for the monkey receptor (IC₉₀=1700 nM) by 95-fold in the presence of 40% serum^[1].
In Vivo: Relugolix (oral administration; 1-3 mg/kg; single dose for pharmacokinetic study) exhibits a good pharmacokinetic profile and obvious suppressive effects of circulating LH levels in monkeys at a dose of 1 mg/kg. The pharmacokinetic profile exhibits with 16.0 ng/mL, 2.7 h, and 90.1 ng for C_max, T_max, and AUC_o, respectively in male cynomolgus monkeys^[1].
Relugolix (oral administration; 3, 10 or 30 mg/kg; twice daily; 4 weeks) significantly decreases the testis weight, and reduces the ventral prostate weight at 3 mg/kg and decreases it to castrate levels at 10 mg/kg in male hGNRHR-knock-in mice^[2].
Relugolix (oral administration; 30, 100 or 200 mg/kg; twice daily; 4 weeks) induces constant diestrous phases in all mice within the first week at 100 mg/kg, and significantly decreases the weights of ovaries and uteri at this dose after 4 weeks in female hGNRHR-knock-in mice^[2].