Elagolix是一种高效、选择性、口服活性、短效、非肽类的促性腺激素释放激素受体（GnRHR）拮抗剂（IC50=0.94nM）。
Cas No.:834153-87-6
Sample solution is provided at 25 µL, 10mM.
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Elagolix is a highly potent, selective, orally-active, short-duration, non-peptide antagonist of the gonadotropin-releasing hormone receptor (GnRHR) (IC50=0.94nM) [1]. Elagolix inhibits the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by blocking the endogenous GnRH signaling pathway, thereby reducing the production of estradiol and progesterone[2]. Elagolix has been widely used in various studies to alleviate endometriosis and improve uterine fibroids[3].
In vitro, Elagolix treatment at 100μM for 1h inhibited inositol-1-phosphate accumulation induced by GnRH peptide in HEK293T cells[4]. Treatment with 100nM Elagolix for 48 hours significantly reduced the expression level of COL1A1 and inhibited the MAPK pathway in leiomyoma cells [5].
In vivo, Elagolix treatment via oral administration at a dose of 30mg/kg for 4h reduced the LH levels in castrated male cynomolgus macaques[6].
References:
[1] Kim S M, Lee M, Lee S Y, et al. Discovery of an orally bioavailable gonadotropin-releasing hormone receptor antagonist[J]. Journal of Medicinal Chemistry, 2016, 59(19): 9150-9172.
[2] Lamb Y N. Elagolix: first global approval[J]. Drugs, 2018, 78(14): 1501-1508.
[3] Ciceri S, Colombo D, Fassi E M A, et al. Elagolix Sodium Salt and Its Synthetic Intermediates: A Spectroscopic, Crystallographic, and Conformational Study[J]. Molecules, 2023, 28(9): 3861.
[4] Ciceri S, Fassi E M A, Vezzoli V, et al. Novel non-peptide uracil-derived human gonadotropin-releasing hormone receptor antagonists[J]. European Journal of Medicinal Chemistry, 2024, 279: 116903.
[5] Wright D, Britten J, Malik M, et al. Relugolix and elagolix directly inhibit leiomyoma extracellular matrix production in 2-dimesnional and 3-dimensional cell cultures[J]. F&S Science, 2022, 3(3): 299-308.
[6] Chen C, Wu D, Guo Z, et al. 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-2 H-pyrimidin-1-yl]-1-phenylethylamino} butyrate (Elagolix), a Potent and Orally Available Nonpeptide Antagonist of the Human Gonadotropin-Releasing Hormone Receptor[J]. Journal of medicinal chemistry, 2008, 51(23): 7478-7485.
Elagolix是一种高效、选择性、口服活性、短效、非肽类的促性腺激素释放激素受体（GnRHR）拮抗剂（IC50=0.94nM）[1]。Elagolix通过阻断内源性GnRH信号通路，抑制黄体生成素（LH）和卵泡刺激素（FSH）的分泌，从而减少雌二醇和孕酮的产生[2]。Elagolix已被广泛用于各类研究，以缓解子宫内膜异位症并改善子宫肌瘤 [3]。
在体外，使用100µM的Elagolix处理HEK293T细胞1小时，抑制了GnRH肽诱导的肌醇-1-磷酸积累[4]。使用100nM的Elagolix处理48小时，显著降低了平滑肌瘤细胞中COL1A1的表达水平，并抑制了MAPK通路[5]。
在体内，口服给予30mg/kg剂量的Elagolix 4小时，降低了去势雄性食蟹猴的LH水平[6]。
| Cell experiment [1]: | |
Cell lines | HEK293T cells |
Preparation Method | The cDNA of the wild-type GnRH1R was subcloned into the pcDNA3.1(+) expression vector with the HA signal, and expressed in HEK293T cells. HEK293T cells were seeded in six-well plates at a density of 3×105 cells per well, and the culture medium was Dulbecco modified Eagle medium supplemented with 10% fetal bovine serum. The cells were pre-treated with Elagolix (100μM) for 1 hour, and then stimulated with the GnRH peptides for 1 hour. The optical density values (OD) were read at 450nm. |
Reaction Conditions | 100μM; 1h |
Applications | Elagolix treatment inhibited inositol-1-phosphate accumulation induced by GnRH peptide in HEK293T cells. |
| Animal experiment [2]: | |
Animal models | Male cynomolgus macaques |
Preparation Method | A total of six male cynomolgus macaques, aged approximately 3.7-6.5 years, underwent complete testicular resection. Drug administration was carried out at least 4 weeks after the surgery. No sedation was administered to the macaques during the administration, but macaques were temporarily confined outside the cage. A single oral administration of 30mg/kg dose of Elagolix was given, blood samples were collected before and 4 hours after administration to determine the concentration of bioactive LH in the serum samples. |
Dosage form | 30mg/kg for once; p.o. |
Applications | Elagolix treatment reduced the LH levels in castrated male cynomolgus macaques. |
References: | |
| Cas No. | 834153-87-6 | SDF | |
| 别名 | 恶拉戈利,NBI-56418 | ||
| 化学名 | (R)-4-((2-(5-(2-fluoro-3-methoxyphenyl)-3-(2-fluoro-6-(trifluoromethyl)benzyl)-4-methyl-2,6-dioxo-2,3-dihydropyrimidin-1(6H)-yl)-1-phenylethyl)amino)butanoic acid | ||
| Canonical SMILES | O=C(CCCN[C@@H](CN(C1=O)C(N(C(C)=C1C2=CC=CC(OC)=C2F)CC3=C(C=CC=C3F)C(F)(F)F)=O)C4=CC=CC=C4)O | ||
| 分子式 | C32H30F5N3O5 | 分子量 | 631.59 |
| 溶解度 | DMSO : ≥ 100 mg/mL (158.33 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5833 mL | 7.9165 mL | 15.8331 mL |
| 5 mM | 316.7 μL | 1.5833 mL | 3.1666 mL |
| 10 mM | 158.3 μL | 791.7 μL | 1.5833 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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