Relugolix

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Relugolix
Relugolix structure.png
Relugolix molecule ball.png
Clinical data
Trade namesRelumina
SynonymsRVT-601; TAK-385
Routes of
administration
By mouth
Drug classGnRH antagonist
Identifiers
CAS Number
PubChem CID
PubChem SID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC29H27F2N7O5S
Molar mass623.630 g/mol g·mol−1
3D model (JSmol)

Relugolix, sold under the brand name Relumina, is a gonadotropin-releasing hormone antagonist (GnRH antagonist) medication which is used in the treatment of uterine fibroids in Japan.[1][2] It is also under development for use in other countries and for the additional indications of endometriosis and prostate cancer.[1][3][4][5][6][7][8] Unlike most other GnRH modulators, but similarly to elagolix (brand name Orilissa), relugolix is a non-peptide and small-molecule compound and is orally active.[7][8] As of February 2019, it is in phase III clinical trials for endometriosis and prostate cancer.[1] The medication was approved for use for the treatment of uterine fibroids in Japan in January 2019.[1][9] A New Drug Application of relugolix for uterine fibroids is expected to be submitted in the United States late 2019.[1]

Medical uses[edit]

Relugolix is approved in Japan for the treatment of uterine fibroids (uterine leiomyoma) in women.[1][2]

Available forms[edit]

Relugolix is available in the form of 40 mg oral tablets.[9][2]

Pharmacology[edit]

Pharmacodynamics[edit]

Relugolix is a selective antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (IC50 = 0.12 nM).[7][8][10]

A single oral administration of relugolix at a dose of 3 mg/kg has been found to suppress luteinizing hormone (LH) levels for more than 24 hours in castrated cynomolgus monkeys, supporting a long duration of action.[7] The medication (80–160 mg/day) has been found to reduce testosterone levels to sustained castrate levels in men with once-daily administration.[10] Lower dosages (10–40 mg/day) are being studied in the treatment of endometriosis and uterine fibroids to achieve partial sex hormone suppression.[5] 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.[5][11]

History[edit]

Relugolix was first described in 2004.[12][7] It superseded sufugolix (developmental code name TAK-013), which was developed by the same researchers.[7] Relugolix was approved for the treatment of uterine fibroids in Japan on 8 January 2019.[1][9] It was the second orally active GnRH antagonist to be introduced for medical use, following elagolix (brand name Orilissa) in July 2018.[1][13]

Society and culture[edit]

Generic names[edit]

Relugolix is the generic name of the drug and its INN, USAN, and JAN.[14][15] It is also known by its former developmental code names RVT-601 and TAK-385.[1][14]

Brand names[edit]

Relugolix is marketed under the brand name Relumina.[1][9][2]

Availability[edit]

Relugolix is available in Japan.[1][9][2]

Research[edit]

Relugolix is under development by Myovant Sciences and Takeda for the treatment of uterine fibroids in countries besides Japan such as the United States.[1] Myovant Sciences intends to submit a New Drug Application of relugolix for uterine fibroids in the United States in the fourth quarter of 2019.[1] Relugolix is also under development for the treatment of endometriosis and prostate cancer in the United States, Japan, and other countries.[1] As of February 2019, it is in phase III clinical trials for these indications.[1]

See also[edit]

References[edit]

  1. ^ a b c d e f g h i j k l m n o http://adisinsight.springer.com/drugs/800028257
  2. ^ a b c d e "Relumina (relugolix) Information - ASKA Pharmaceutical" (PDF) (in Japan). ASKA Pharmaceutical. January 2019. Retrieved 16 February 2019.CS1 maint: Unrecognized language (link)
  3. ^ Goenka L, George M, Sen M (June 2017). "A peek into the drug development scenario of endometriosis - A systematic review". Biomed. Pharmacother. 90: 575–585. doi:10.1016/j.biopha.2017.03.092. PMID 28407578.
  4. ^ Dellis A, Papatsoris A (October 2017). "Therapeutic outcomes of the LHRH antagonists". Expert Rev Pharmacoecon Outcomes Res. 17 (5): 481–488. doi:10.1080/14737167.2017.1375855. PMID 28870102.
  5. ^ a b c Streuli I, de Ziegler D, Borghese B, Santulli P, Batteux F, Chapron C (March 2012). "New treatment strategies and emerging drugs in endometriosis". Expert Opin Emerg Drugs. doi:10.1517/14728214.2012.668885. PMID 22439891.
  6. ^ 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.
  7. ^ a b c d e f Miwa K, Hitaka T, Imada T, Sasaki S, Yoshimatsu M, Kusaka M, Tanaka A, Nakata D, Furuya S, Endo S, Hamamura K, Kitazaki T (July 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". J. Med. Chem. 54 (14): 4998–5012. doi:10.1021/jm200216q. PMID 21657270.
  8. ^ a b c Nakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, Sasada R, Takeyama M, Miwa K, Watanabe T, Kusaka M (January 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". Eur. J. Pharmacol. 723: 167–74. doi:10.1016/j.ejphar.2013.12.001. PMID 24333551.
  9. ^ a b c d e https://www.prnewswire.com/news-releases/myovant-provides-corporate-updates-and-reports-financial-results-for-third-fiscal-quarter-ended-december-31-2018-300791994.html
  10. ^ a b MacLean D, Shi H, Suri A, Faessel H, and Saad F (2013). "Safety and Testosterone-Lowering Effects of the Investigational, Oral, GnRH Antagonist, TAK-385 in Healthy Male Volunteers: Results of a Phase 1 Inpatient/Outpatient Study". doi:10.1210/endo-meetings.2013.CN.1.SAT-318.
  11. ^ Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP (February 2009). "Suppression of gonadotropins and estradiol in premenopausal women by oral administration of the nonpeptide gonadotropin-releasing hormone antagonist elagolix". J. Clin. Endocrinol. Metab. 94 (2): 545–51. doi:10.1210/jc.2008-1695. PMC 2646513. PMID 19033369.
  12. ^ https://patents.google.com/patent/US7300935/
  13. ^ https://adisinsight.springer.com/drugs/800020238
  14. ^ a b https://chem.nlm.nih.gov/chemidplus/rn/737789-87-6
  15. ^ https://www.kegg.jp/entry/D10888

Further reading[edit]

External links[edit]