ERD-1233
ERD-1233 is an orally active ERα PROTAC degrader with a DC50 of 0.9 nM. ERD-1233 exhibits plasma stability and microsomal stability across multiple species, and shows no significant inhibitory effect on major cytochrome P450 subtypes and hERG channels. ERD-1233 inhibits tumor growth and degrades ERα protein levels in xenograft tumor models, with favorable biosafety. ERD-1233 can be used in breast cancer-related research.
(Pink: Estrogen Receptor/ERR ligand (HY-201580); Blue: Cereblon ligand (HY-W1009348); Black: linker (HY-W889109)).
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Formel: C49H53N5O6
- Molecular Weight:807.98
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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ERα 0.9 nM (DC50) |
ERD-1233 (12 h) potently degrades ERα in MCF-7 human breast cancer cells, with a DC50 of 0.9 nM, and achieves a complete (100%) maximum degradation effect[1].
ERD-1233 (0.3-10 nM; 14-22 h) potently degrades ERα in MCF-7 and T47D human breast cancer cells[1].
ERD-1233 (1 μM) exhibits excellent plasma and microsomal stability across multiple species, with a plasma half-life of over 240 min and a microsomal half-life of over 60 min[1].
ERD-1233 (5 min CYP3A4, 10 min CYP2B6) does not inhibit major human CYP enzymes at concentrations up to 10 μM, indicating a low potential for drug-drug interactions mediated by CYP inhibition[1].
At the highest tested concentration of 30 μM, ERD-1233 (5 min) shows an IC50 value greater than 30 μM for hERG channel inhibition, indicating a low risk of inducing arrhythmia[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MCF-7 cells and T47D cells
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Concentration:0.3, 1, 3, 10, 30 and 100 nM
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Incubation Time:14 h (MCF-7 cells); 22 h (T47D cells)
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Result:The compound effectively reduced ER protein levels in a dose-dependent manner in both cell lines. It achieved DC50 values of approximately 1 nM and exhibited a maximum degradation (Dmax) of roughly 75% at concentrations ranging from 3 to 10 nM in both cell lines.
ERD-1233 (10-20 mg/kg; p.o.; once daily; for 4 consecutive weeks) induces regression of ER wild-type MCF-7 xenograft tumors in female SCID mice, and the efficacy at the 20 mg/kg dose is superior to that of ARV-471 at 30 mg/kg[1].
ERD-1233 (10 mg/kg; p.o.; single administration) reduces the protein level of ESR1Y537S mutant ERα by up to 78% in MCF-7 xenograft tumors of female SCID mice[1].
ERD-1233 (30 mg/kg; p.o.; once daily, 5 days per week; 2 weeks) induces tumor regression in ESR1Y537S-mutant MCF-7 xenografts in female SCID mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice (female; ER wild-type MCF-7 xenograft model, received 17β-Estradiol in drinking water, injected with 10 million MCF-7 cells in 50% Matrigel subcutaneously)[2]
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Dosage:3 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:p.o.; once daily; 3 days
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Result:Reduced ERα protein levels in tumors by 42% at 6 h and 43% at 24 h at 3 mg/kg.
Reduced ERα protein levels in tumors by 62% at 6 h and 50% at 24 h at 10 mg/kg.
Increased drug concentrations in both plasma and tumor tissue in a dose-proportional manner when dose was increased from 3 to 10 mg/kg.
Showed low drug levels present at 24 h, indicating no drug accumulation.
Achieved tumor regression of 34% at 10 mg/kg and 68% at 20 mg/kg.
Showed greater efficacy at 20 mg/kg than ARV-471 at 30 mg/kg (p = 0.01).
Induced minimal animal weight losses or other signs of toxicity during the experiment.
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Animal Model:SCID mice (female; ESR1^Y537S mutant MCF-7 xenograft model, no 17β-Estradiol treatment, injected with 10 million ESR1^Y537S MCF-7 cells in 50% Matrigel subcutaneously)[2]
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Dosage:PD study: 10 mg/kg (single oral dose); Efficacy study: 5 mg/kg (first 2 weeks, once daily, 5 days/week, p.o.) 30 mg/kg (last 2 weeks, once daily, 5 days/week, p.o.), and 10 mg/kg (once daily, 5 days/week, p.o.) throughout.
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Administration:p.o.; single dose or daily, 5 days a week; 4 weeks total
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Result:Reduced mutant ERα protein levels in tumors by 43% at 3 h and 78% at 24 h.
Achieved a plasma concentration of 5365 ng/mL and a tumor concentration of 312 ng/mL at 3 h.
Achieved a plasma concentration of 16 ng/mL and a tumor concentration of 157 ng/mL at 24 h.
Effectively inhibited tumor growth throughout the experiment at 10 mg/kg.
Displayed minimal antitumor activity after 2 weeks at 5 mg/kg.
Achieved tumor regression during the subsequent 2-week treatment period when switched from 5 mg/kg to 30 mg/kg.
Chemical Information
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Molecular Weight 807.98
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Formel C49H53N5O6
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SMILES
OC1=CC=C2[C@@H](C3=CC=C(N4CCC5(CC4)CC(CN6C[C@H]7N(CC6)C(C(OC7)=C8CN9[C@@H]%10C(NC(CC%10)=O)=O)=CC=C8C9=O)CO5)C=C3)[C@@H](C%11=CC=CC=C%11)CCC2=C1
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
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Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
ERD-1233 Related Classifications
HY-169367 Related Classifications
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