RAD1901 selectively binds to and degrades the ER and is a potent antagonist of ER-positive breast cancer cell proliferation. RAD1901 treatment exhibits dose-dependent inhibition of ERα expression, with an EC50 of 0.6 nM. Treatment of ER-positive MCF-7 cells with E2 results in a potent and dose-dependent increase in proliferation, with an EC50 of 4 pM. Treatment of cells with RAD1901 in the presence of 10 pM E2 resultsin a dose-dependent decrease in proliferation, with an IC50 value of 4.2 nM.
RAD1901 produces a robust and profound inhibition of tumor growth in MCF-7 xenograft models. RAD1901-treated animals survived longer than those treated with either control or fulvestrant. RAD1901 preserves ovariectomy-induced bone loss and preventes the uterotropic effects of E2.
RAD1901 is serially diluted in ES2 screening buffer to concentrations ranging from 10 to 10-6 μM. Aliquots (25 μL) of each dilution are added to a black 384-well microtiter plate, in triplicate. The ER–Fluormone complex is prepared as directed, with 2 nM Fluormone ES2 and 30 nM ER. A 25 μL aliquot of this preparation is added to each reaction well. The plates are sealed and incubated in the dark at room temperature for 4 h. Polarization values for each well are measured and plotted against the concentration of the test compound. The IC50 is determined from at least three independent experiments, with E2 serving as a positive control[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
