Reactome | GNRHR binds chemical antagonists

GNRHR binds chemical antagonists

Stable Identifier

R-HSA-9718379

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

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Gonadotropin-releasing hormone (GNRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal axis. GNHR binding to GNRH receptors causes the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.

The non-peptide GNRHR antagonist drug elagolix (Chen et al. 2008) is indicated for the treatment of moderate to severe endometriosis pain (Lamb 2018, Surrey et al. 2018, Taylor et al. 2019). The non-peptide GNRHR antagonist drug relugolix (Miwa et al. 2011) is used in the treatment of prostate cancer in men (Shore et al. 2020) and uterine fibroids in women (Barra et al. 2019). Linzagolix is a new non-peptide GNRHR antagonist under development for the treatment of uterine fibroids, endometriosis, and adenomyosis (Donnez & Donnez 2020, Donnez et al. 2020).

Literature References

PubMed ID	Title	Journal	Year
19006286	Discovery of sodium R-(+)-4-{2-[5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-[trifluoromethyl]benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenylethylamino}butyrate (elagolix), a potent and orally available nonpeptide antagonist of the human gonadotropin-releasing hormone receptor Chen, C, Wu, D, Guo, Z, Xie, Q, Reinhart, GJ, Madan, A, Wen, J, Chen, T, Huang, CQ, Chen, M, Chen, Y, Tucci, FC, Rowbottom, M, Pontillo, J, Zhu, YF, Wade, W, Saunders, J, Bozigian, H, Struthers, RS	J. Med. Chem.	2008
21657270	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 Miwa, K, Hitaka, T, Imada, T, Sasaki, S, Yoshimatsu, M, Kusaka, M, Tanaka, A, Nakata, D, Furuya, S, Endo, S, Hamamura, K, Kitazaki, T	J Med Chem	2011