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Purity: ≥98%
Elagolix (formerly NBI56418; ABT620; NBI-56418; ABT-620; trade name: Orilissa) is a potent, specific, orally bioavailable, non-peptide antagonist of the gonadotropin-releasing hormone receptor (GnRHR) used for pain management. It inhibits GnRHR with a Kd of 54 pM. Elagolix was given FDA approval on July 23, 2018, to treat endometriosis-related moderate to severe pain. A short-acting GnRH antagonist, elagolix suppresses ovarian estrogen production in a dose-dependent manner, resulting in partial suppression at lower doses and complete suppression at higher doses. Because Elagolix is non-peptide and readily absorbed through the mouth, it is considered the leader of a new class of GnRH inhibitors known as second-generation inhibitors.
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| Enzyme Assay |
Elagolix, a non-peptide, oral bioavailable, strong, selective, and KD of 54 pM, is an antagonist of the gonadotropin-releasing hormone receptor (GnRHR). It was formerly known as NBI56418 and ABT-620; trade name: Orilissa. The FDA approved Elagolix on July 23, 2018, for the treatment of moderate to severe endometriosis-related pain. Elagolix is a short-acting GnRH antagonist that suppresses ovarian estrogen production in a dose-dependent manner, meaning that higher doses result in full suppression while lower doses only cause partial suppression. Elagolix's non-peptide structure and oral bioavailability make it the leader of a new class of GnRH inhibitors known as second-generation inhibitors.
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion
The Tmax of elagolix is reported as being 1.0 hours. The effect of a high-fat meal (relative to fasting) can result in a reduction of the AUC and Cmax by as much as 24% and 36%, respectively. The primary route of elimination of elagolix is via hepatic metabolism. The apparent volume of distribution at steady state (Vdss/F) of elagolix is reported to be 1674 for a 150 mg daily regimen and 881 for a 200 mg twice daily regimen. The oral clearance (CL/F) of elagolix is 123 L/hr for a 150 mg once daily regimen and 144 L/hr for a 200 mg twice daily regimen. Metabolism / Metabolites Elagolix is predominantly metabolized by the CYP3A family of isoenzymes despite participating in minor metabolic pathways with the CYP2D6, CYP2C8, and uridine glucuronosyl transferases (UGTs) enzymes as well. The primary metabolite of elagolix, referred to as NBI-61962 (R-(+)-4-{2-[5-(2-fluoro-3-hydroxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino}-butyrate), is not believed to possess any significant biologic activity due to its low plasma exposure and an observed potency that is exceptionally less than the parent elagolix compound (Ki value of 3.5 compared to 0.9 nM). Biological Half-Life The terminal phase elimination half-life of elagolix is recorded as being 4 to 6 hours. |
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| Toxicity/Toxicokinetics |
Hepatotoxicity
Elagolix therapy has been associated with serum enzyme elevations in a small proportion of patients, rates of ALT elevations above 3 times the upper limit of normal being 0.2% with 150 mg once daily and 1.1% with 200 mg twice daily. The elevations, however, are generally mild and self-limited, resolving even without dose adjustment. Occasional patients require drug discontinuation because of serum enzyme elevations, but there were no instances of liver injury with jaundice or clinically apparent acute liver injury in the preregistration-controlled trials. Since its approval and more widescale use, there have been no published reports of clinically apparent liver injury attributed to elagolix. Likelihood score: E (unlikely cause of clinically apparent liver injury). Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of elagolix during breastfeeding. Elagolix is 80% protein bound, has a half-life of 4 to 6 hours, and it is a peptide that is likely digested in the infant's gastrointestinal tract, so it is unlikely to reach clinically important levels in infant serum. However, because no information is available on the use of elagolix during breastfeeding caution should be used, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding The percentage bound to human plasma proteins for elagolix has been documented as 80%. |
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| Additional Infomation |
Pharmacodynamics
During a three menstrual cycle study in healthy women, an elagolix 150 mg once daily regimen and a 200 mg twice daily regimen resulted in an ovulation rate of about 50% and 32%, respectively. In Phase 3 trials in women with endometriosis, elagolix caused a dose-dependent reduction in median estradiol concentrations to approximately 42 pg/mL for the 150 mg once daily regimen and 12 pg/mL for the 200 mg twice daily regimen. Furthermore, the effect of elagolix on the QTc interval was investigated in a randomized, placebo- and positive-controlled, open-label, single-dose, crossover thorough QTc study in 48 healthy adult premenopausal women. Elagolix concentrations in subjects administered a single dose of 1200 mg was seventeen times higher than the concentration in subjects given elagolix 200 mg twice daily. Nevertheless, there was no clinically relevant prolongation of the QTc interval. |
| Molecular Formula |
C32H30F5N3O5
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| Molecular Weight |
631.59
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| Exact Mass |
631.21
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| Elemental Analysis |
C, 60.85; H, 4.79; F, 15.04; N, 6.65; O, 12.67
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| CAS # |
834153-87-6
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| Related CAS # |
Elagolix sodium; 832720-36-2
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| PubChem CID |
11250647
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
728.6±70.0 °C at 760 mmHg
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| Flash Point |
394.5±35.7 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.567
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| LogP |
7.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
45
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| Complexity |
1080
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1N(CC2C(F)=CC=CC=2C(F)(F)F)C(=O)N(C[C@@H](C2C=CC=CC=2)NCCCC(=O)O)C(=O)C=1C1C=CC=C(OC)C=1F
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| InChi Key |
EAUOKZIVMZVQL-VWLOTQADSA-N
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| InChi Code |
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
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| Chemical 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
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.96 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5833 mL | 7.9165 mL | 15.8331 mL | |
| 5 mM | 0.3167 mL | 1.5833 mL | 3.1666 mL | |
| 10 mM | 0.1583 mL | 0.7917 mL | 1.5833 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03271489 | Active Recruiting |
Other: Elagolix Placebo Drug: Elagolix |
Heavy Menstrual Bleeding Uterine Fibroids |
AbbVie | September 13, 2017 | Phase 3 |
| NCT04630990 | Active Recruiting |
N/A | Endometriosis | AbbVie | December 14, 2020 | N/A |
| NCT04856306 | Active Recruiting |
Drug: Elagolix Oral Product Other: Groups 1 and 2 myomectomy and uterine artery embolization, respectively, are surgical/procedure |
Heavy Menstrual Bleeding Fibroid Uterus |
Medstar Health Research Institute |
April 12, 2021 | N/A |
| NCT06076486 | Recruiting | Drug: Elagolix Drug: Elagolix placebo |
Endometriosis | Nanjing Chia-tai Tianqing Pharmaceutical |
September 14, 2023 | Phase 3 |
| NCT05648669 | Recruiting | Drug: Elagolix Drug: Elagolix placebo |
Endometriosis | Qilu Pharmaceutical (Hainan) Co., Ltd. |
September 4, 2022 | Phase 3 |
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