Elagolix sodium
[CAS# 832720-36-2]

Identification

• Classification: API >> Other chemicals
• Name: Elagolix sodium
• Synonyms: NBI 56418NA
• Molecular Formula: C₃₂H₂₉F₅N₃O₅.Na
• Molecular Weight: 653.57
• CAS Registry Number: 832720-36-2
• EC Number: 692-765-8
• SMILES: CC1=C(C(=O)N(C(=O)N1CC2=C(C=CC=C2F)C(F)(F)F)C[C@@H](C3=CC=CC=C3)NCCCC(=O)[O-])C4=C(C(=CC=C4)OC)F.[Na+]

Safety Data

• Hazard Symbols: GHS07;GHS08 Danger
• Risk Statements: H304-H319-H360-H361
• Safety Statements: P203-P264+P265-P280-P301+P316-P305+P351+P338-P318-P331-P337+P317-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Aspiration hazard	Asp. Tox.	1	H304
Reproductive toxicity	Repr.	2	H361
Eye irritation	Eye Irrit.	2	H319
Reproductive toxicity	Repr.	1B	H360
Reproductive toxicity	Repr.	1A	H360
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412

Discovery and Applications

Elagolix sodium is the sodium salt form of elagolix, an orally active, non-peptide gonadotropin-releasing hormone (GnRH) receptor antagonist. It is used primarily in the management of hormone-dependent conditions such as endometriosis and uterine fibroids. The molecular formula of elagolix sodium is C₃₂H₂₉F₃N₄NaO₅, reflecting its complex structure that includes fluorinated aromatic rings and heterocyclic components designed for receptor binding and bioavailability.

Elagolix was developed to provide a more flexible and reversible suppression of the hypothalamic-pituitary-gonadal axis compared to traditional GnRH agonists. By competitively binding to GnRH receptors in the pituitary gland, elagolix sodium inhibits the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to a decrease in ovarian sex hormone production, mainly estrogen and progesterone. This hormonal suppression alleviates symptoms caused by estrogen-dependent diseases such as pelvic pain associated with endometriosis.

The compound's discovery emerged from efforts to develop small-molecule GnRH antagonists with improved oral bioavailability and safety profiles. Elagolix sodium's design incorporates modifications to optimize receptor affinity, metabolic stability, and pharmacokinetic properties allowing once or twice daily oral dosing.

Pharmacokinetically, elagolix sodium is rapidly absorbed after oral administration, with peak plasma concentrations typically achieved within one to two hours. It is metabolized primarily by cytochrome P450 enzymes, particularly CYP3A4, and is excreted mainly via the feces. The drug has a half-life of approximately four to six hours, supporting its dosing schedule.

Clinically, elagolix sodium is indicated for the management of moderate to severe pain associated with endometriosis and, in some regions, for the treatment of heavy menstrual bleeding associated with uterine fibroids. Its ability to reduce estrogen levels without causing complete hypoestrogenism offers an advantage in minimizing side effects such as bone loss and vasomotor symptoms.

Adverse effects reported with elagolix sodium use include hot flushes, headache, nausea, and decreased bone mineral density with long-term use. Monitoring is recommended during therapy, especially in patients with risk factors for osteoporosis.

In summary, elagolix sodium is an orally active GnRH receptor antagonist designed to modulate reproductive hormone levels for the treatment of estrogen-dependent gynecological conditions. Its chemical structure and pharmacological profile provide effective symptom relief with a manageable safety profile.

References

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. Journal of Medicinal Chemistry, 51(23).
DOI: 10.1021/jm8006454

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 and Metabolism, 94(2).
DOI: 10.1210/jc.2008-1695

2024. The short- and mid-term efficacy and safety of elagolix in the management of pain associated with endometriosis: A systematic review and meta-analysis. Journal of Gynecology Obstetrics and Human Reproduction, 53(7).
DOI: 10.1016/j.jogoh.2024.102829