1349723-93-8
1349723-93-8 structure
- Name: Elacestrant dihydrochloride
- Chemical Name: RAD1901 HCl salt
- CAS Number: 1349723-93-8
- Molecular Formula: C30H40Cl2N2O2
- Molecular Weight: 531.557
- Catalog: Research Areas Cancer
- Create Date: 2017-03-08 07:09:54
- Modify Date: 2024-01-02 14:56:32
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Elacestrant dihydrochloride (RAD1901 dihydrochloride) is a selective and orally available estrogen receptor (ERR) degrader with IC50 values of 48 and 870 nM for ERα and ERβ, respectively.
| Name | RAD1901 HCl salt |
|---|---|
| Synonyms |
2-Naphthalenol, 6-[2-[ethyl[[4-[2-(ethylamino)ethyl]phenyl]methyl]amino]-4-methoxyphenyl]-5,6,7,8-tetrahydro-, (6R)-, hydrochloride (1:2)
(6R)-6-[2-(Ethyl{4-[2-(ethylamino)ethyl]benzyl}amino)-4-methoxyphenyl]-5,6,7,8-tetrahydro-2-naphthalenol dihydrochloride Elacestrant dihydrochloride |
| Description | Elacestrant dihydrochloride (RAD1901 dihydrochloride) is a selective and orally available estrogen receptor (ERR) degrader with IC50 values of 48 and 870 nM for ERα and ERβ, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 48 nM (ERα), 870 nM (ERβ)[1] |
| In Vitro | 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[1]. |
| In Vivo | 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[1]. |
| Kinase Assay | 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]. |
| Cell Assay | For proliferation assays, MCF-7 cells are treated with 2% charcoal-stripped FBS–MEM containing 10 pM E2 with either RAD1901 or additional E2 at concentrations ranging from 10-9 to 1 M. The medium is removed after 48 h of incubation and the cells are lysed by adding 100 μl of CellTiter Glo. The plates are gently mixed on a plate shaker for 10 min before the luminescent signal is measured on a luminometer. The EC50 and IC50of the test compound are then defined[1]. |
| Animal Admin | Mice: RAD1901 is stored as a dry powder, formulated for use as a homogenous suspension in 0.5% (w/v) methylcellulose in deionized water. Fourteen days after tumor cell implantation, the mice are randomized into nine groups of 15 animals each and treated with vehicle, tamoxifen (1 mg/animal every other day), fulvestrant (0.5 mg/animal daily), or RAD1901 (0.3, 1, 3, 10, 30, 60, 90, and 120 mg/kg daily). Tumor volumes are evaluated twice per week[1]. |
| References |
| Molecular Formula | C30H40Cl2N2O2 |
|---|---|
| Molecular Weight | 531.557 |
| Exact Mass | 530.246704 |