Elagolix

Elagolix
Systematic (IUPAC) name
4-[[(1R)-2-[5-(2-fluoro-3-methoxyphenyl)-3-[[2-fluoro-6-(trifluoromethyl)phenyl]methyl]-4-methyl-2,6-dioxopyrimidin-1-yl]-1-phenylethyl]amino]butanoic acid
Clinical data
Routes of
administration		 Oral
Pharmacokinetic data
Biological half-life 2.4–6.3 hours[1]
Identifiers
CAS Number 834153-87-6
832720-36-2 (sodium)
ATC code H01CC02 (WHO)
PubChem CID 11250647
ChemSpider 9425680
Synonyms Elagolix sodium, NBI-56418, ABT-620
Chemical data
Formula C32H30F5N3O5
Molar mass 631.589716 g/mol

Elagolix (INN, USAN) (former developmental code names NBI-56418, ABT-620) is a highly potent, selective, orally-active, short-duration, non-peptide antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (KD = 54 pM) that is under development for clinical use by Neurocrine Biosciences and AbbVie.[2][3] As of 2015, it is in phase III clinical trials for the treatment of endometriosis and uterine leiomyoma.[1] 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. Elagolix is regarded as the frontrunner of a new class of GnRH inhibitors that have been denoted as second-generation, due to their non-peptide nature and oral bioavailability.[1]

Because of the relatively short half-life of elagolix, the actions of gonadotropin-releasing hormone (GnRH) are not fully blocked throughout the day.[1][4] For this reason, gonadotropin and sex hormone levels are only partially suppressed, and the degree of suppression can be dose-dependently adjusted, as desired.[1][4] Moreover, if elagolix is discontinued, its effects are rapidly reversible.[1][4] Due to the suppression of estrogen levels by elagolix being incomplete, effects on bone mineral density are minimal, which is in contrast to first-generation GnRH inhibitors.[5][6] Moreover, the incidence and severity of menopausal side effects such as hot flashes are also reduced relative to first-generation GnRH inhibitors.[1][4]

See also

References

  1. 1 2 3 4 5 6 7 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. ↑ 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.
  3. ↑ 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.
  4. 1 2 3 4 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: 2646513. PMID 19033369.
  5. ↑ 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.
  6. ↑ 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. PMID 25249568.

External links


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