Elagolix

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Elagolix
Elagolix.svg
Clinical data
Synonyms NBI-56418; ABT-620
Routes of
administration
By mouth
Drug class GnRH analogue; GnRH antagonist; antigonadotropin
Pharmacokinetic data
Elimination half-life 2.4–6.3 hours[1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
Formula C32H30F5N3O5
Molar mass 631.590 g/mol
3D model (JSmol)

Elagolix (INN, USAN) (former developmental code names NBI-56418, ABT-620) is a gonadotropin-releasing hormone antagonist (GnRH antagonist), developed for clinical use by Neurocrine Biosciences and AbbVie.[2][3][4] As of 2017, it is in preregistration for the treatment of endometriosis and is in phase III clinical trials for the treatment of uterine leiomyoma.[1][2] The drug was also under investigation for the treatment of prostate cancer and benign prostatic hyperplasia, but development for these indications was ultimately not pursued.[2] Elagolix is the first of a new class of GnRH modulators that have been denoted as "second-generation" due to their small-molecule structure and oral activity.[1]

Elagolix acts as a potent, selective, orally active, non-peptide antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (KD = 54 pM).[3][4] Because of the relatively short biological half-life of elagolix, the actions of gonadotropin-releasing hormone (GnRH) are not fully blocked throughout the day with once-daily administration.[1][5] For this reason, gonadotropin and sex hormone levels are only partially suppressed, and the degree of suppression can be dose-dependently adjusted as needed (e.g., with twice-daily dosing).[1][5] In addition, because of its short duration in the body, if elagolix is discontinued, its effects are rapidly reversible.[1][5] In relation to the partial and incomplete suppression of estrogen levels, adverse effects of elagolix on bone mineral density are minimal, which is in contrast to first-generation GnRH modulators.[6][7] Moreover, the incidence and severity of menopausal side effects such as hot flashes are also reduced relative to first-generation GnRH modulators.[1][5]

See also[edit]

References[edit]

  1. ^ a b c d e f g Ezzati, Mohammad; Carr, Bruce R (2015). "Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain". Women's Health. 11 (1): 19–28. doi:10.2217/whe.14.68. ISSN 1745-5057. 
  2. ^ a b c AdisInsight: Elagolix.
  3. ^ a b 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 (2008). "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". J. Med. Chem. 51 (23): 7478–85. doi:10.1021/jm8006454. PMID 19006286. 
  4. ^ a b Thomas L. Lemke; David A. Williams (24 January 2012). Foye's Principles of Medicinal Chemistry. Lippincott Williams & Wilkins. pp. 1411–. ISBN 978-1-60913-345-0. 
  5. ^ a b c d Struthers RS, Nicholls AJ, Grundy J, Chen T, Jimenez R, Yen SS, Bozigian HP (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 2646513Freely accessible. PMID 19033369. 
  6. ^ Diamond MP, Carr B, Dmowski WP, Koltun W, O'Brien C, Jiang P, Burke J, Jimenez R, Garner E, Chwalisz K (2014). "Elagolix treatment for endometriosis-associated pain: results from a phase 2, randomized, double-blind, placebo-controlled study". Reprod Sci. 21 (3): 363–71. doi:10.1177/1933719113497292. PMID 23885105. 
  7. ^ Carr B, Dmowski WP, O'Brien C, Jiang P, Burke J, Jimenez R, Garner E, Chwalisz K (2014). "Elagolix, an oral GnRH antagonist, versus subcutaneous depot medroxyprogesterone acetate for the treatment of endometriosis: effects on bone mineral density". Reprod Sci. 21 (11): 1341–51. doi:10.1177/1933719114549848. PMC 4212335Freely accessible. PMID 25249568. 

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