Elagolix

Elagolix, sold under the brand name Orilissa, is a gonadotropin-releasing hormone antagonist (GnRH antagonist) medication which is used in the treatment of pain associated with endometriosis in women. It is also under development for the treatment of uterine fibroids and heavy menstrual bleeding in women. The medication was under investigation for the treatment of prostate cancer and enlarged prostate in men as well, but development for these conditions was discontinued. Elagolix is taken by mouth once or twice per day. It can be taken for up to 6 to 24 months, depending on the dosage.

Elagolix
Clinical data
Pronunciation/ˌɛləˈɡoʊlɪks/
EL-ə-GOH-liks
Trade namesOrilissa, Oriahnn
Other namesNBI-56418, ABT-620
AHFS/Drugs.comMonograph
MedlinePlusa618044
License data
Pregnancy
category
  • Contraindicated
Routes of
administration		By mouth
Drug classGnRH antagonist
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityLow (5.8% in rats, 11% in monkeys; no human data)
Protein binding80%
MetabolismLiver (CYP3A)
Elimination half-lifeTypical: 4–6 hours
Single dose: 2.4–6.3 hrs
Continuous: 2.2–10.8 hours
ExcretionUrine: <3%
Feces: 90%
Identifiers
  • 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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.259.758
Chemical and physical data
FormulaC32H30F5N3O5
Molar mass631.600 g·mol−1
3D model (JSmol)
  • COc1cccc(-c2c(C)n(Cc3c(F)cccc3C(F)(F)F)c(=O)n(C[C@H](NCCCC(=O)O)c3ccccc3)c2=O)c1F
  • InChI=1S/C32H30F5N3O5/c1-19-28(21-11-6-14-26(45-2)29(21)34)30(43)40(18-25(20-9-4-3-5-10-20)38-16-8-15-27(41)42)31(44)39(19)17-22-23(32(35,36)37)12-7-13-24(22)33/h3-7,9-14,25,38H,8,15-18H2,1-2H3,(H,41,42)/t25-/m0/s1
  • Key:HEAUOKZIVMZVQL-VWLOTQADSA-N

Side effects of elagolix include menopausal-like symptoms such as hot flashes, night sweats, insomnia, amenorrhea, mood changes, anxiety, and decreased bone density, among others. Elagolix is a GnRH antagonist, or an antagonist of the gonadotropin-releasing hormone receptor (GnRHR), the biological target of the hypothalamic hormone gonadotropin-releasing hormone (GnRH). By blocking the GnRHR, it dose-dependently suppresses the gonadal production and hence circulating levels of sex hormones such as estradiol, progesterone, and testosterone. Elagolix is a short-acting GnRH antagonist, and can be used to achieve either partial or more substantial suppression of sex hormone levels. Reduced estrogen levels in the endometrium are responsible for the efficacy of elagolix in the treatment of endometriosis.

Elagolix was first described in 2008 and was approved for medical use in July 2018. It has been described as a "second-generation" GnRH modulator due to its non-peptide and small-molecule nature and its oral activity. Unlike GnRH agonists and older GnRH antagonists, which are peptides and first-generation GnRH modulators, elagolix is not a GnRH analogue as it is not structurally related to GnRH. Elagolix was the first second-generation and orally active GnRH modulator to be introduced for medical use. The introduction of elagolix in the United States and Canada was followed by that of relugolix (brand name Relumina), the next second-generation GnRH antagonist, in Japan in January 2019. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

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