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)).
For research use only. We do not sell to patients.
- Formula: C49H53N5O6
- Molecular Weight:807.98
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All PROTACs Isoforms
More
Biological Activity
Description
IC50 & Target
[1]|
ERα 0.9 nM (DC50) |
In Vitro
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. Further protocols information, click here.
-
Cell Line:MCF-7 cells and T47D cells
-
Concentration:0.3, 1, 3, 10, 30 and 100 nM
-
Incubation Time:14 h (MCF-7 cells); 22 h (T47D cells)
-
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.
Parmacokinetics
In Vivo
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.
-
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]
-
Dosage:3 mg/kg; 10 mg/kg; 20 mg/kg
-
Administration:p.o.; once daily; 3 days
-
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.
-
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]
-
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.
-
Administration:p.o.; single dose or daily, 5 days a week; 4 weeks total
-
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
-
Molecular Weight 807.98
-
Formula C49H53N5O6
-
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
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
Patient-Derived Xenograft (PDX)
Patient-derived xenograft (PDX) models are generated by engrafting primary human tumor tissue directly into immunodeficient mice, allowing in vivo propagation of patient tumor biology without initial in vitro adaptation. These models are used to preserve key histopathological and molecular characteristics of the original tumor and enable assessment of tumor growth dynamics and therapeutic response in a living organism. The biological readout is tumor engraftment and subsequent growth in the murine host, which reflects the ability of human tumor cells to survive, vascularize, and expand in an immunocompromised microenvironment.
-
Patient-Derived Orthotopic Xenograft (PDOX)
Patient-derived orthotopic xenograft (PDOX) modeling implants fresh patient tumor tissue or patient-derived tumor cells into the anatomically corresponding organ or tissue site of immunodeficient mice, usually by surgical orthotopic implantation, to preserve patient tumor histology, local microenvironmental context, invasion, metastatic behavior, and treatment-response features better than subcutaneous implantation. PDOX readouts include tumor engraftment, orthotopic tumor growth, local invasion, metastasis, recurrence after resection, histologic similarity to the donor tumor, biomarker retention, molecular concordance, survival, and response or resistance to therapy. PDOX models are used for preclinical drug testing and individualized therapy evaluation, but engraftment success varies by tumor type and specimen quality.
-
Splenic/Portal-Vein Liver Metastasis Xenograft
Splenic and portal-vein liver metastasis xenograft models deliver tumor cells into the portal circulation so that cells reach the liver first and form hepatic metastatic lesions; splenic injection uses the spleen as an access route to the portal system, while direct portal-vein injection introduces cells into the portal vein without requiring splenectomy. The assay detects liver colonization, intrahepatic tumor growth, tumor distribution, treatment response, survival, and liver-metastasis microenvironment changes; readouts include bioluminescence or fluorescence imaging, gross liver nodule counts, liver weight or tumor burden, histology, and survival.
-
Subcutaneous Cell-Line-Derived Xenograft
Subcutaneous cell-line-derived xenograft (CDX) models are established by implanting cultured human cancer cell lines into immunodeficient mice, where the injected cells form localized tumors that can be monitored in vivo as a measure of tumorigenic potential, growth kinetics, and treatment response. These models are widely used in oncology research because they allow reproducible tumor formation and enable comparative assessment of tumor growth between different cell lines or genetic manipulations in a controlled in vivo microenvironment. Subcutaneous implantation of cancer cells in immunodeficient mice is a standard approach for evaluating tumor growth behavior and therapeutic response across multiple cancer types, including prostate, esophageal, pancreatic, and colon cancer models.
-
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.
-
Orthotopic Cell-Line Xenograft
Orthotopic cell-line xenograft models involve implantation of human cancer cell lines into the anatomically corresponding organ of immunodeficient mice to reproduce tumor growth within a native microenvironment, enabling more clinically relevant tumor behavior compared with subcutaneous models. These models are widely used because orthotopic placement better recapitulates tumor progression, including invasion and metastatic spread, which are often underrepresented in heterotopic implantation systems. Compared with conventional xenografts, orthotopic implantation is described as more technically complex but provides improved simulation of tumor-microenvironment interactions and metastatic behavior, making it particularly valuable for translational oncology research. Surgical orthotopic implantation approaches have been emphasized as enabling faithful reproduction of clinical cancer features, including metastasis and disease progression patterns that align with the tumor’s organ of origi
-
Intraperitoneal/Peritoneal Dissemination Xenograft
Intraperitoneal (IP) or peritoneal dissemination xenograft models are based on the introduction of human cancer cells into the peritoneal cavity of immunodeficient mice, where they attach to peritoneal surfaces, form multicellular aggregates or spheroids, and progressively generate disseminated tumor nodules that mimic advanced peritoneal metastatic disease. These models are widely used to study ovarian cancer progression, tumor-microenvironment interactions, and intraperitoneal therapeutic responses, often incorporating bioluminescence or fluorescence imaging to longitudinally monitor tumor burden in vivo. The biological principle relies on the capacity of tumor cells such as SKOV3 or related ovarian carcinoma lines to survive in suspension, aggregate within ascites-like fluid, adhere to mesothelial surfaces, and invade peritoneal organs, thereby recapitulating human peritoneal carcinomatosis patterns observed in advanced disease.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)