ERD-12310A
ERD-12310A is an orally active ERα PROTAC degrader, with a Ki value of 0.95 nM against human ERα and a DC50 of 47 pM for ERα in MCF-7 cells. ERD-12310A forms a ternary complex with ERα and the CRBN E3 ubiquitin ligase, thereby inducing ubiquitination and proteasomal degradation of wild-type and ESR1Y537S mutant ERα. ERD-12310A induces tumor regression in ER+ breast cancer xenografts and inhibits tumor growth in ESR1Y537S mutant breast cancer xenografts. ERD-12310A can be used in studies related to ER-positive breast cancer and ESR1-mutant breast cancer.
(Pink: ERα ligand (HY-164925); Blue: Cereblon ligand (HY-168055); Black: linker).
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- CAS No.: 3026007-23-5
- Formule: C51H56N4O6
- Masse moléculaire:821.01
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Activité biologique
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hERα 0.95 nM (Ki) |
ERα 47 pM (DC50) |
ERD-12310A potently and efficiently degrades ERα in MCF-7 cells with a DC50 of 47 pM and Dmax of 103%, and is 10 times more potent than ARV-471[1][2].
ERD-12310A (0.3-10 nM; 4 h) potently degrades ERα in MCF-7 and T47D cells, achieving maximum degradation at 1 nM (4 h) in MCF-7 cells and 10 nM (4 h) in T47D cells[2].
ERD-12310A (10-100 nM; 7 h) degrades >80% of wild-type, ERαY537S mutant, and ERαD538G mutant ERα protein in MCF-7 cell lines at 10 nM and 100 nM following a 7 h treatment, with degradation dependent on cereblon binding[2].
ERD-12310A (5 nM; 4 h, with 2 h pretreatment of blocking agents) mediated ERα degradation in MCF-7 cells requires binding to ERα and cereblon, and is dependent on neddylation and proteasome activity[2].
ERD-12310A (0.5-500 nM; 5 h) does not significantly degrade the neo-substrate GSPT1 in MCF-7 cells at concentrations from 0.5 nM to 500 nM over 5 h, despite potently degrading ERα[2].
ERD-12310A (range of concentrations) potently inhibits MCF-7 cell growth, with activity primarily driven by ERα degradation, and shows a hook effect at 1 μM[2].
ERD-12310A binds to purified human ERα protein with a Ki of 0.95 nM[2].
ERD-12310A (1 μM; 0-60 min) has excellent stability in human, rat, and mouse liver microsomes, with a T1/2 of >60 min across all species[2].
ERD-12310A weakly inhibits most human CYP isoforms (IC50 >10 μM) and moderately inhibits CYP2B6 (IC50 = 2.5 μM) and CYP2C19 (IC50 = 6.0 μM)[2].
ERD-12310A (range of concentrations) is a very weak hERG channel inhibitor, with IC50 >10 μM and 43.7% inhibition observed at 10 μM[2].
ERD-12310A exhibits high plasma protein binding, with 98.9%, 95.7%, and 99.0% bound in human, rat, and mouse plasma, respectively[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:ER+ MCF-7 and T47D human breast cancer cell lines
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Concentration:0.3 nM (MCF-7); 1 nM (MCF-7); 3 nM (T47D); 10 nM (T47D)
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Incubation Time:4 h
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Result:Reduced ERα protein levels at 0.3 nM and achieved maximum degradation at 1 nM with a 4 h treatment in MCF-7 cells.
Significantly reduced ERα protein levels at 3 nM and achieved maximum degradation at 10 nM with a 4 h treatment in T47D cells.
Was 3-10 times more potent than ARV-471 in both cell lines.
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Cell Line:ER+ wild-type MCF-7, MCF-7 Y537S mutant, and MCF-7 D538G mutant human breast cancer cell lines
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Concentration:10 nM; 100 nM
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Incubation Time:7 h
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Result:Reduced wild-type ERα protein levels by >80% at both 10 nM and 100 nM with a 7 h treatment.
Reduced Y537S and D538G mutant ERα protein levels by >80% at both 10 nM and 100 nM with a 7 h treatment.
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Cell Line:ER+ MCF-7 human breast cancer cell line
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Concentration:0.5 nM; 5 nM; 50 nM; 500 nM
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Incubation Time:5 h
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Result:Showed minimal effect on GSPT1 protein levels across all tested concentrations.
Potently degraded ERα protein levels in a dose-dependent manner.
Control GSPT1 degrader MG-277 effectively reduced GSPT1 levels but had no effect on ERα.
| Species | Dose | Route | Vss | CL | AUC0-∞ | Cmax | T1/2 | F |
|---|---|---|---|---|---|---|---|---|
| Mice[2] | 1 mg/kg | i.v. | 5.8 L/kg | 18.8 mL/min/kg | / | / | / | / |
| Mice[2] | 3 mg/kg | p.o. | / | / | 979 ng·h/mL | 58.6 ng/mL | 13.3 h | 37 % |
| Rat[2] | 1 mg/kg | i.v. | 1.9 L/kg | 9.7 mL/min/kg | / | / | / | / |
| Rat[2] | 3 mg/kg | p.o. | / | / | 583 ng·h/mL | 57.7 ng/mL | 5.6 h | 10 % |
| Dog[2] | 1 mg/kg | i.v. | 3.2 L/kg | 2.1 mL/min/kg | / | / | / | / |
| Dog[2] | 3 mg/kg | p.o. | / | / | 15118 ng·h/mL | 469.4 ng/mL | 23.2 h | 49 % |
ERD-12310A (5-30 mg/kg; p.o.; 5 days a week; 5 weeks) achieves strong tumor growth inhibition (75% TGI at 10 mg/kg) and complete tumor growth inhibition at an escalated dose in the MCF-7 ESR1Y537S mutant ER xenograft model following 5 weeks of intermittent daily oral administration[2].
ERD-12310A (10-30 mg/kg; p.o.; daily; 3 days) achieves sustained reduction of wild-type ER protein (66-72% depletion) in MCF-7 xenograft tumors 24 hours after 3 days of daily oral administration at 10-30 mg/kg[2].
ERD-12310A (10-30 mg/kg; p.o.; single dose; daily; 3 days) achieves significant depletion of ESR1Y537S mutant ER protein (71-74% reduction) in MCF-7 xenograft tumors 24 hours after a single 10 mg/kg oral dose or 3 days of daily oral dosing at 10-30 mg/kg[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice[2]
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Dosage:3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 5 weeks
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Result:Achieved 93% tumor growth inhibition (TGI).
Achieved 94% TGI.
Achieved tumor regression with 110% TGI at the end of treatment (day 81).
Caused no significant weight loss or toxicity symptoms throughout the experiment.
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Animal Model:SCID mice[2]
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Dosage:10 mg/kg; 5 mg/kg (for 3 weeks) followed by 30 mg/kg (for 2 weeks)
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Administration:p.o.; 5 days a week; 5 weeks
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Result:Achieved 75% TGI after 5 weeks of treatment at 10 mg/kg.
Completely inhibited tumor growth during the treatment period at the escalated dose (5 mg/kg for 3 weeks, then 30 mg/kg for 2 weeks).
Caused no significant weight loss or toxicity symptoms throughout the experiment.
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Animal Model:SCID mice[2]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; daily; 3 days
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Result:Reduced wild-type ER protein levels by 69% in tumor tissue at 10 mg/kg at the 24-hour time point after the last dose.
Reduced wild-type ER protein levels by 72% in tumor tissue at 30 mg/kg at the 24-hour time point after the last dose.
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Animal Model:SCID mice[2]
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Dosage:10 mg/kg (single dose); 10 mg/kg (daily for 3 days); 30 mg/kg (daily for 3 days)
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Administration:p.o.; single dose; daily; 3 days
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Result:Reduced ESR1Y537S protein levels by 71% in tumor tissue at 24 hours after a single 10 mg/kg dose.
Reduced ESR1Y537S protein levels by 74% in tumor tissue at 24 hours after the last dose of daily 10 mg/kg dosing for 3 days.
Reduced ESR1Y537S protein levels by 74% in tumor tissue at 24 hours after the last dose of daily 30 mg/kg dosing for 3 days.
Chemical Information
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CAS No. 3026007-23-5
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Masse moléculaire 821.01
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Formule C51H56N4O6
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SMILES
O=C(N1)[C@H](CCC1=O)N(C2=O)CC3=C2C=CC4=C3OCC45CCN(CC5)C[C@H]6COC7(CC6)CCN(CC7)C8=CC=C(C=C8)[C@H]9[C@H](CCC%10=C9C=CC(O)=C%10)C%11=CC=CC=C%11
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Peng R, et al. Development of PROTACs targeting estrogen receptor: an emerging technique for combating endocrine resistance. RSC medicinal chemistry. 2025 Mar 19;16(3):1023-1036. [Content Brief]
[2]. Rej RK, et al. Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα). Journal of medicinal chemistry. 2024 Dec 12;67(23):20933-20965. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ERD-12310A Related Classifications
HY-164924 Related Classifications
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