(A–C) Halo-618 fluorescence measured every 4 hr in T47D cells expressing WT halo-ERα (A), Y537S (B), and D538G (C) treated over 100 hr with vehicle (Veh), 1 μM estradiol (E2), fulvestrant (ICI), or …
Ligand and mutational influences on estrogen receptor alpha (ERα) cellular turnover after 24 hr.
Data were normalized by cell count. Antiestrogens are categorized as stabilizers if their maximum signal for WT ERα at 5 µM is greater than 1.5, neutral if between 0.9 and 1.1, and degrader if less than 0.9 in this assay.
Data are representative of the mean of three replicates ± standard error.
Data are representative of three replicates per concentration ± SD. All data were normalized to actin control in the individual treatments.
Data are shown as the mean of 3 replicates ± SD.
(A) Chemical structures of Laso and the synthesized stereospecific methyl derivatives. (B) Dose-response curves of hormone (E2) alongside LASOLaso and derivatives after 24 hr treatment for WT …
(A) Chromatogram of LA-Deg chiral separation. (B) Purification of the LA-Deg peak 1. (C) Purification of LA-Deg peak 2. (D) Chromatogram of LA-Stab chiral separation. (E) Purification of LA-Stab …
(A), LA-Stab (B), or LA-Deg (C) for 24 hours. Data shown are the mean of 3 replicates ± SD.
SUMOylation of WT (A), Y537S (B), or D538G (C) ERα in the presence of vehicle, fulvestrant, GDC0927, raloxifene, AZD9496, 4-hydroxytamoxifen (4OHT), lasofoxifene-degrader (LA-Deg), or …
Ligand and Mutational Influences on Estrogen Receptor SUMOylation.
The SEM values for IC50s were all within 20% except for Ral with WT (21.4%) and OHT for D538G (26.2%).
IC50 of SRC1 receptor interacting domain binding to WT and mutant estrogen receptor alpha.
The SEM values for IC50s were all within 50% except for D538G with AZD9496 (52%).
(A), Y537S (B), and D538G (C) estrogen receptor alpha in the presence and absence of 5 nM estradiol (E2). Data are mean of three biological replicates ± SD.
Selective estrogen receptor modulators (SERMs) in (A) WT, (B) WT/Y537S, and (C) WT/D538G MCF7 cells. SERM/selective estrogen receptor degraders/downregulators (SERDs) in (D) WT, (E) WT/Y537S, (F) …
Ligand and mutational influences on estrogen receptor alpha reporter gene transcription after 24 hr.
Data were normalized by cell count.
Ishikawa cells treated with representative selective estrogen receptor modulators (SERM) or selective estrogen receptor degraders/downregulators (SERD) for 3 days in the absence of E2 and assayed …
Selective estrogen receptor modulator-agonist activities in uterine epithelial cells measured by induction of alkaline phosphatase.
(A) 4-hydroxytamoxifen (4OHT). (B) Fulvestrant (ICI). (C) Lasofoxifene (Laso). (D) Lasofoxifene-Stabilizer (LA-Stab). (E) Lasofoxifene-Degrader (LA-Deg). (F) Normalized cell count after 84 hr. All …
(A) Superposition of each monomer in the asymmetric unit of WT (green) or Y537S (cyan) ERα LBD in complex with RAL. (B) 2mFo-DFc difference map (yellow mesh) of the electron density around E380 …
X-ray crystal structure data collection and refinement statistics.
Average main chain B-factors are shown at each H12 position normalized to average B-factor for each Y537S estrogen receptor alpha LBD structure. Lower B-factor indicates less mobility within the …
(A) Y537S-BZA. (B) WT-RAL. (C) Y537S-RAL. (D) Y537S-4OHT. (E) WT-LA-Deg. (F) Y537S-LA-Deg. (G) WT-LA-Stab. (H) Y537S-LA-Stab. (I) WT-RU39411. (J) Y537S-RU39411. (K) WT-Clomiphene. (L) Y537S-LSZ102. …