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]。