Elacestrant dihydrochloride (RAD1901 dihydrochloride) is a novel, orally bioavailable selective estrogen receptor (ER) degrader with IC50 of 48nM and 870nM for ERα and ERβ, respectively. Estrogen and estrogen receptor (ER) are important drivers of breast tumorigenesis and breast cancer progression. Elacestrant dihydrochloride can specifically bind to and degrade estrogen receptors, making it a potent antagonist of estrogen receptor-positive breast cancer cell proliferation[1].
In vitro, treatment with Elacestrant dihydrochloride (10⁻15–10⁻6M; 48h) dose-dependently inhibited MCF-7 cell proliferation in the presence of 10pM E₂, with an IC₅₀ value of 4.2nM[1]. Elacestrant dihydrochloride (0-1µM; 24 or 48h) dose-dependently induced estrogen receptor (ER) degradation and inhibited estrogen-mediated signaling and growth in multiple ER+ cell lines, including MCF-7 and T47D[2].
In vivo, oral administration of Elacestrant dihydrochloride (0.1, 0.3, 1, and 3mg/kg/d; 4 weeks) produced a dose-dependent and statistically significant suppression of ovariectomy-induced bone loss in female SD rats[1]. Elacestrant dihydrochloride (0.01-10mg/kg/d; p.o.; 3 days) dose-dependently reversed E₂ (0.01mg/kg)-induced uterine stimulation, including increases in uterine wet weight and endometrial epithelial thickness[1]. Elacestrant dihydrochloride (0.3, 1, 3, 10, 30, and 120mg/kg/day; p.o.; 40 days) dose-dependently inhibited tumor growth in the MCF-7 xenograft model, with no adverse effect on body weight[1]. Elacestrant dihydrochloride (120mg/kg/d; p.o.; 54 days) effectively crossed the blood-brain barrier and significantly prolonged survival in the MCF-7 intracranial xenograft mouse model[1].
References:
[1] Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G. RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models. Anticancer Drugs. 2015;26(9):948-956.
[2] Bihani T, Patel HK, Arlt H, et al. Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Clin Cancer Res. 2017;23(16):4793-4804.