Relugolix

Relugolix
Systematic (IUPAC) name
1-[4-[1-[(2,6-difluorophenyl)methyl]-5-[(dimethylamino)methyl]-3-(6-methoxypyridazin-3-yl)-2,4-dioxothieno[2,3-d]pyrimidin-6-yl]phenyl]-3-methoxyurea
Clinical data
Routes of
administration		 Oral
Identifiers
CAS Number 737789-87-6
ATC code H01CC02 (WHO)
PubChem CID 10348973
ChemSpider 8524431
Synonyms TAK-385
Chemical data
Formula C29H27F2N7O5S
Molar mass 623.630386 g/mol

Relugolix (INN) (developmental code name TAK-385) is a non-peptide, orally-active, selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (IC50 = 0.12 nM)[1] that is under development for clinical use by Takeda.[2][3] It is currently in phase II clinical trials for the treatment of endometriosis, uterine leiomyoma, and prostate cancer.[1][3][4][5]

A single oral administration of relugolix at a dose of 3 mg/kg has been found to suppress luteinizing hormone levels for more than 24 hours in castrated cynomolgus monkeys, indicating a long duration of action.[2] The drug (80–160 mg/day) has been found to reduce testosterone levels to sustained castrate levels in men with once-daily chronic administration.[1] Lower dosages (10–40 mg/day) are being studied in the treatment of endometriosis and uterine leiomyoma to achieve partial sex hormone suppression.[4] The reasoning behind partial suppression for these conditions is to reduce the incidence and severity of menopausal symptoms such as hot flushes and to avoid bone mineral density changes caused by estrogen deficiency that can eventually lead to osteoporosis.[4][6]

See also

References

  1. 1 2 3 http://press.endocrine.org/doi/abs/10.1210/endo-meetings.2013.CN.1.SAT-318
  2. 1 2 Miwa, Kazuhiro; Hitaka, Takenori; Imada, Takashi; Sasaki, Satoshi; Yoshimatsu, Mie; Kusaka, Masami; Tanaka, Akira; Nakata, Daisuke; Furuya, Shuichi; Endo, Satoshi; Hamamura, Kazumasa; Kitazaki, Tomoyuki (2011). "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". Journal of Medicinal Chemistry 54 (14): 4998–5012. doi:10.1021/jm200216q. ISSN 0022-2623. PMID 21657270.
  3. 1 2 Nakata, Daisuke; Masaki, Tsuneo; Tanaka, Akira; Yoshimatsu, Mie; Akinaga, Yumiko; Asada, Mari; Sasada, Reiko; Takeyama, Michiyasu; Miwa, Kazuhiro; Watanabe, Tatsuya; Kusaka, Masami (2014). "Suppression of the hypothalamic–pituitary–gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: Studies in human GnRH receptor knock-in mice". European Journal of Pharmacology 723: 167–174. doi:10.1016/j.ejphar.2013.12.001. ISSN 0014-2999.
  4. 1 2 3 Streuli, Isabelle; de Ziegler, Dominique; Borghese, Bruno; Santulli, Pietro; Batteux, Frédéric; Chapron, Charles (2012). "New treatment strategies and emerging drugs in endometriosis". Expert Opinion on Emerging Drugs 17 (1): 83–104. doi:10.1517/14728214.2012.668885. ISSN 1472-8214.
  5. ↑ Elancheran, R.; Maruthanila, V. L.; Ramanathan, M.; Kabilan, S.; Devi, R.; Kunnumakara, A.; Kotoky, Jibon (2015). "Recent discoveries and developments of androgen receptor based therapy for prostate cancer". Med. Chem. Commun. 6 (5): 746–768. doi:10.1039/C4MD00416G. ISSN 2040-2503.
  6. ↑ Struthers, R. Scott; Nicholls, Andrew J.; Grundy, John; Chen, Takung; Jimenez, Roland; Yen, Samuel S. C.; Bozigian, Haig P. (2009). "Suppression of Gonadotropins and Estradiol in Premenopausal Women by Oral Administration of the Nonpeptide Gonadotropin-Releasing Hormone Antagonist Elagolix". The Journal of Clinical Endocrinology & Metabolism 94 (2): 545–551. doi:10.1210/jc.2008-1695. ISSN 0021-972X. PMC: 2646513. PMID 19033369.

External links


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