Elagolix Sodium

Catalog No.S4896 Batch:S489601

Technical Data

Formula	C₃₂H₂₉F₅N₃O₅.Na
Molecular Weight	653.57	CAS No.	832720-36-2
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (153.0 mM)
		Water	100 mg/mL (153.0 mM)
		Ethanol	100 mg/mL (153.0 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Elagolix Soidum (NBI-56418, ABT-620) is a potent, selective, orally active, non-peptide antagonist of the gonadotropin-releasing hormone receptor (GnRHR) with Kd value of 54 pM. Concentration at 10 μM shows no significant activity on ion channels, enzymes, and transporters (inhibition <50%).

Targets

GnRHR ^[1]
(Cell-free assay)

54 pM(Kd)

In vitro

Elagolix displays high affinity in a competition binding assay for hGnRH-R (Ki = 0.90 nM) and low CYP3A4 inhibition (IC50 = 56 μM). It is a slowly disassociating antagonist exhibiting very high affinity (KD = 54 pM) and insurmountable antagonism. Elagolix is highly selective at hGnRH-R, its wider receptor selectivity is tested at a concentration of 10 μM in a panel of radioligand binding assays for 100 off-target receptors, ion channels, enzymes, and transporters, and significant activity is not observed (inhibition <50%). It does not stimulate histamine release from cultured rat peritoneal mast cells. Elagolix lacks the necessary high binding affinity to the rat GnRH receptor (Ki = 4400 nM) and it possesses high affinity at the monkey GnRH receptor (Ki = 3.3 nM)^[1].

In vivo

Oral administration of Elagolix suppresses luteinizing hormone in castrated macaques. Elagolix shows good efficacy in suppressing luteinizing hormone in monkeys and exhibits high oral bioavailability in dogs (~100% when dosed via oral gavage at 50 mg/kg)^[1].

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines RBL-1 cells stably expressing the human cloned GnRH receptor Concentrations -- Incubation Time 1 h Method RBL-1 cells stably expressing the human cloned GnRH receptor are seeded into 96 well plates at a density of 15 000 cells per well in inositol-free DMEM containing 10% dialyzed FBS, 10 mM HEPES, 2 mM L-glutamine, 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, and 50 μg/mL penicillin/streptomycin and are labeled for 48 h with 0.2 μCi myo-2-[3H]inositol. The cells are washed once in PBS and pretreated with assay buffer (140 mM NaCl, 4 mM KCl, 20 mM HEPES, 8.3 mM glucose, 1 mM MgCl2, 1 mM CaCl2, 10 mM LiCl, and 0.1% BSA) for 15-60 min at 37 °C. The cells are then stimulated with GnRH (6 nM) in the presence or absence of antagonist and incubated for 60 min at 37℃. Cells are extracted with 10 mM formic acid at 4℃ for 30 min, and the lysate is loaded onto Millipore plates containing 20 μg of Dowex AG1-X8 resin. The plate is washed once in H2O and once in 60 mM ammonium formate/5 mM sodium tetraborate, and inositol phosphates are eluted with 1 M ammonium formate/0.1 M formic acid. The eluate is transferred to a Lumaplate and counted in a TopCount NXT.
Animal Study:^{^[1]}	Animal Models Rhesus Monkey Dosages 10 and 50 mg/kg (oral); 3 and 10 mg/kg (i.v.) Administration p.o. or i.v.

Cell Assay:^{^[1]}

Cell lines
RBL-1 cells stably expressing the human cloned GnRH receptor
Concentrations
--
Incubation Time
1 h
Method
RBL-1 cells stably expressing the human cloned GnRH receptor are seeded into 96 well plates at a density of 15 000 cells per well in inositol-free DMEM containing 10% dialyzed FBS, 10 mM HEPES, 2 mM L-glutamine, 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, and 50 μg/mL penicillin/streptomycin and are labeled for 48 h with 0.2 μCi myo-2-[3H]inositol. The cells are washed once in PBS and pretreated with assay buffer (140 mM NaCl, 4 mM KCl, 20 mM HEPES, 8.3 mM glucose, 1 mM MgCl2, 1 mM CaCl2, 10 mM LiCl, and 0.1% BSA) for 15-60 min at 37 °C. The cells are then stimulated with GnRH (6 nM) in the presence or absence of antagonist and incubated for 60 min at 37℃. Cells are extracted with 10 mM formic acid at 4℃ for 30 min, and the lysate is loaded onto Millipore plates containing 20 μg of Dowex AG1-X8 resin. The plate is washed once in H2O and once in 60 mM ammonium formate/5 mM sodium tetraborate, and inositol phosphates are eluted with 1 M ammonium formate/0.1 M formic acid. The eluate is transferred to a Lumaplate and counted in a TopCount NXT.

Animal Study:^{^[1]}

Animal Models
Rhesus Monkey
Dosages
10 and 50 mg/kg (oral); 3 and 10 mg/kg (i.v.)
Administration
p.o. or i.v.

References

[1] Chen C, et al. J Med Chem. 2008, 51(23):7478-85.

Selleck's Elagolix Sodium has been cited by 3 publications

Heat promotes melanogenesis by increasing the paracrine effects in keratinocytes via the TRPV3/Ca2+/Hh signaling pathway [ iScience, 2023, 26(5):106749]	PubMed: 37216091
Gonadotropin-releasing hormone receptor inhibits triple-negative breast cancer proliferation and metastasis [ J Int Med Res, 2022, 50(3):3000605221082895]	PubMed: 35264044
Structure of the human gonadotropin-releasing hormone receptor GnRH1R reveals an unusual ligand binding mode [ Nat Commun, 2020, 11(1):5287]	PubMed: 33082324

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SHIPPING AND STORAGE
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