Relugolix

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Relugolix 是一种口服非肽促性腺激素释放激素（GnRH 或黄体生成素释放激素 (LHRH)）拮抗剂，具有潜在的抗肿瘤活性。

Relugolix, also known as TAK-385, is a luteinizing hormone-releasing hormone (LH-RH) receptor antagonist administered orally. By preventing LH-RH from binding with the LH-RH receptor in the anterior pituitary gland and suppressing the secretion of luteinizing hormone (LH) and follicle stimulation hormone (FSH) from the anterior pituitary gland, TAK-385 controls the effect of LH and FSH on the ovary, reduces the level of estrogen in blood, which is known to be associated with the development of endometriosis and uterine fibroids, and is expected to improve the symptoms of these disorders.(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.(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 Cmax, Tmax, and AUCo, respectively in male cynomolgus monkeys.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.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.

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.

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 Cmax, Tmax, and AUCo, respectively in male cynomolgus monkeys.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.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. Animal Model:Male hGNRHR-knock-in mice Dosage:3, 10 or 30 mg/kg Administration:Oral administration; 3, 10 or 30 mg/kg; twice daily; 4 weeksResult:Decreased testicular function.Animal Model:Female hGNRHR-knock-in miceDosage:30, 100 or 200 mg/kg Administration:Oral administration; 30, 100 or 200 mg/kg; twice daily; 4 weeks Result:Suppressed the hypothalamic–pituitary–gonadal axis to gonadectomized levels.Downregulated GnRH receptor mRNA levels in the pituitary.

TAK385 | TAK-385 | TAK 385 | Relugolix

Apoptosis

MDM2-p53

GNRHR

Cancer

——

737789-87-6

623.63

C29H27F2N7O5S

>98% (HPLC)

DMSO : 50 mg/mL. 80.18 mM;

CN(C)Cc1c(sc2c1c(=O)n(c(=O)n2Cc1c(cccc1F)F)c1nnc(cc1)OC)c1ccc(cc1)NC(=O)NOC

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

(-20℃)

With Ice Pack

≥ 2 years