ERα/RAD51 degrader 1
ERα/RAD51 degrader 1 is a ERα and RAD51 HyT degrader as well as an apoptosis (Apoptosis) inducer. ERα/RAD51 degrader 1 induces conformational changes in helices 11-12 of ERα, promotes the recruitment of Hsp70, and drives the degradation of ERα and RAD51 via the ubiquitin-proteasome pathway. ERα/RAD51 degrader 1 downregulates the expression of BRCA1/2. ERα/RAD51 degrader 1 acts on tamoxifen (HY-13757A)-sensitive and tamoxifen-resistant breast cancer in both in vitro and in vivo models. ERα/RAD51 degrader 1 is applicable to breast cancer-related research (hydrophobic tag: (HY-B0402)).
For research use only. We do not sell to patients.
- Formula: C39H41F3N2O7S
- Molecular Weight:738.81
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
IC50 & Target
[1]|
HSP70 |
ERα |
In Vitro
ERα/RAD51 degrader 1 (Compound 20a) inhibits the viability of LCC2 cells after 72 h, with an IC50 value of 7.727 μM[1].
ERα/RAD51 degrader 1 (0.5-15 μM; 3-48 h) induces dose- and time-dependent proteasomal degradation of ERα in MCF-7, T47D and LCC2 breast cancer cells, a process driven by Hsp70-mediated ubiquitination[1].
ERα/RAD51 degrader 1 (1-10 μM; 24 h) induces G1-phase cell cycle arrest in Tamoxifen (HY-13757A)-resistant LCC2 breast cancer cells[1].
ERα/RAD51 degrader 1 (1-20 μM; 48-72 h) induces apoptosis in MCF-7, T47D, and tamoxifen-resistant LCC2 breast cancer cells in a dose-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:MCF-7, T47D, LCC2
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Concentration:1-10 μM
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Incubation Time:24 h
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Result:Increased G1 phase proportion from 66.0% (control) to 79.3% (10 μM), while reducing S phase proportion.
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Cell Line:MCF-7, T47D, LCC2
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Concentration:1-20 μM
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Incubation Time:72 h (flow cytometry); 48 h (Western blot)
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Result:Dose-dependently increased apoptosis in MCF-7 cells.
Dose-dependently increased apoptosis in T47D cells.
Increased apoptosis in LCC2 cells.
Parmacokinetics
| Species | Dose | Route | Bioavailability |
|---|---|---|---|
| Rat[1] | 5 mg/kg | i.p. | 33 % |
In Vivo
ERα/RAD51 degrader 1 (2.5-5 mg/kg; i.p.; once every 2 days) inhibits tumor growth of LCC2 breast cancer xenografts, with the 5 mg/kg dose exhibiting superior efficacy to Fulvestrant and no organ toxicity observed[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude (female, 4-week-old, subcutaneous xenograft of MCF-7 cells, estradiol valerate supplementation)[1]
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Dosage:5 mg/kg
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Administration:i.p.; every 2 days
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Result:Reduced tumor volume and weight more effectively than fulvestrant.
Reduced Ki67 (cell proliferation marker) in tumor tissues.
Showed no significant abnormalities or damage in heart, liver, spleen, and kidney tissues via H&E staining.
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Animal Model:BALB/c nude (female, 4-week-old, subcutaneous xenograft of tamoxifen-resistant LCC2 cells, estradiol valerate supplementation)[1]
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Dosage:2.5 mg/kg; 5 mg/kg
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Administration:i.p.; every 2 days
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Result:Effectively inhibited tumor growth at both 2.5 mg/kg and 5 mg/kg doses.
Outperformed fulvestrant at the 5 mg/kg dose.
Reduced Ki67 (cell proliferation marker) in tumor tissues.
Showed no significant abnormalities or damage in heart, liver, and kidney tissues via H&E staining.
Chemical Information
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Molecular Weight 738.81
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Formula C39H41F3N2O7S
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SMILES
O=S(N(C1=CC=C(C=C1)OCCC(NC23C[C@H](C[C@@H](C4)C3)C[C@H]4C2)=O)CC(F)(F)F)(C5C[C@@H]6C(C7=CC=C(O)C=C7)=C(C8=CC=C(O)C=C8)[C@H]5O6)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
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Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)