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| Other Sizes |
| Targets |
ERα 4.6 nM (IC50)
ERα degrader-2 targets estrogen receptor alpha (ERα), functioning as a selective estrogen receptor degrader (SERD). It exhibits potent binding affinity for ERα with an IC₅₀ of 17.1 nM. The compound induces degradation of ERα protein with an EC₅₀ of 0.3 nM, effectively eliminating the receptor from cells. By degrading ERα, the compound disrupts estrogen-mediated signaling pathways that drive the growth and survival of ER-positive breast cancer cells. It can be used for HER-positive breast cancer research. The compound shows high selectivity for ERα over other related targets. |
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| ln Vitro |
ERα degrader-2 (0.01-40 nM) lowers ERα expression and not entirely destroys ERα in MCF-7 cells even at a higher biological dose in MCF7 cells[1].
In vitro, ERα degrader-2 demonstrates potent binding affinity for ERα with an IC₅₀ of 17.1 nM and excellent degradation efficacy with an EC₅₀ of 0.3 nM. The compound effectively eliminates ERα protein from cells through targeted degradation, leading to sustained inhibition of ER-dependent gene transcription and cell growth. It exhibits favorable pharmacokinetic properties and excellent drug-like properties in vitro. The compound shows activity in ER-positive breast cancer cell lines, including those with HER-positive status. Its potent degradation activity makes it a valuable tool for studying ERα biology and developing SERD-based therapeutic strategies. |
| ln Vivo |
In mice, ERα degrader-2 (oral; 2–6 mg/kg; QD; 21 days) significantly inhibits tumor growth and reduces tumor volume[1]. The pharmacokinetic parameters of ERα degrader-2 (oral gavage; 2 mg/kg; single dosage) are superior to those of AZD9496. Its half-life period is 12.1 hours, its plasma exposure (AUC) is 16073.7 h*ng/mL, and its oral availability is 80.5%[1].
In vivo, ERα degrader-2 demonstrates significant efficacy in breast cancer xenograft models. Oral administration at doses of 2-6 mg/kg once daily for 21 days exhibits tumor growth inhibition in mice. The compound's favorable pharmacokinetic properties support its in vivo activity. It is effective in HER-positive breast cancer models. The compound's potent ERα degradation activity translates to sustained inhibition of tumor growth in preclinical models. Further studies are needed to fully characterize its efficacy across different breast cancer subtypes and in combination with other therapeutic agents. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ERα degrader-2 typically involve competitive binding experiments using ERα protein and radiolabeled or fluorescently labeled estradiol as tracer to assess binding affinity. The IC₅₀ value of 17.1 nM is determined through dose-response binding experiments. Degradation efficacy is assessed in cell-based assays measuring ERα protein levels by Western blot or immunofluorescence after treatment, with an EC₅₀ of 0.3 nM. Assays are conducted under appropriate conditions with proper controls. Binding affinity and degradation potency are expressed as IC₅₀ and EC₅₀ values, respectively.
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| Cell Assay |
In vitro cell-based assays for ERα degrader-2 utilize ER-positive breast cancer cell lines to assess ERα degradation and anti-proliferative activity. Cells are treated with varying concentrations of the compound for 24-72 hours. ERα protein levels are measured by Western blot or high-content imaging to determine degradation efficacy (EC₅₀ = 0.3 nM). Cell proliferation is assessed using MTT, CCK-8, or BrdU incorporation assays. ER-dependent transcriptional activity is evaluated using reporter gene assays with ERE-luciferase constructs. Standard cell culture conditions (37°C, 5% CO₂) with appropriate media are employed. Dose-response curves are generated to determine IC₅₀ and EC₅₀ values.
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| Animal Protocol |
Animal/Disease Models: MCF-7 human breast cancer xenograft model in nude mice[1]
Doses: 2 mg/kg; 6 mg/kg Route of Administration: Oral administration; 2-6 mg/kg; QD; 21 days Experimental Results: demonstrated in vivo efficacy in breast cancer xenograft model. In vivo animal studies with ERα degrader-2 typically use immunocompromised mice bearing ER-positive breast cancer xenografts. The compound is administered orally once daily at doses of 2-6 mg/kg for 21 days. Endpoints include tumor volume measurements, assessment of ERα protein levels in tumor tissues by immunohistochemistry or Western blot, evaluation of ER-dependent gene expression by qPCR, and pharmacokinetic profiling. The compound demonstrates significant tumor growth inhibition in these models. All procedures must comply with institutional animal care and use guidelines. |
| ADME/Pharmacokinetics |
ERα degrader-2 exhibits favorable pharmacokinetic properties. The compound has a molecular weight of 492.53 g/mol and a molecular formula of C₂₉H₂₇F₃N₂O₂. Its chemical name is 3',5'-difluoro-4'-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1H,2H,3H,4H,9H-pyrido[3,4-b]indol-1-yl]-[1,1'-biphenyl]-4-carboxylic acid. The compound's favorable PK properties support its oral bioavailability and in vivo efficacy. Detailed pharmacokinetic parameters including half-life, Cmax, and AUC are available in preclinical study reports. The compound shows excellent drug-like properties for further development.
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| Toxicity/Toxicokinetics |
Toxicological data for ERα degrader-2 are not extensively documented in the publicly available literature. The compound is intended for research use only and is not approved for human therapeutic applications. Standard safety precautions should be observed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, comprehensive toxicological profiling including acute toxicity, genotoxicity, and organ-specific toxicity studies would be required before any consideration for clinical development. The compound should be handled in well-ventilated areas with proper waste disposal procedures.
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| References | |
| Additional Infomation |
ERα degrader-2 (CAS#: 2235396-63-9) has a molecular formula of C₂₉H₂₇F₃N₂O₂ and a molecular weight of 492.53 g/mol. Its chemical name is 3',5'-difluoro-4'-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1H,2H,3H,4H,9H-pyrido[3,4-b]indol-1-yl]-[1,1'-biphenyl]-4-carboxylic acid. The compound is a selective estrogen receptor degrader (SERD) with potent ERα binding affinity (IC₅₀ = 17.1 nM) and degradation efficacy (EC₅₀ = 0.3 nM). It exhibits favorable pharmacokinetic properties and excellent drug-like properties. It can be used for HER-positive breast cancer research. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C29H27F3N2O2
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|---|---|
| Molecular Weight |
492.53
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| Exact Mass |
492.202
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| CAS # |
2235396-63-9
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| PubChem CID |
135230895
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| Appearance |
Brown to reddish brown solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
36
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| Complexity |
777
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1(C2=CC(F)=C([C@@H]3C4=C(C[C@@H](C)N3CC(F)(C)C)C3=C(N4)C=CC=C3)C(F)=C2)=CC=C(C(O)=O)C=C1
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| InChi Key |
XKYAKCQZMYWSSE-CHAGWJKLSA-N
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| InChi Code |
InChI=1S/C29H27F3N2O2/c1-16-12-21-20-6-4-5-7-24(20)33-26(21)27(34(16)15-29(2,3)32)25-22(30)13-19(14-23(25)31)17-8-10-18(11-9-17)28(35)36/h4-11,13-14,16,27,33H,12,15H2,1-3H3,(H,35,36)/t16-,27-/m1/s1
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| Chemical Name |
4-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]benzoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0303 mL | 10.1517 mL | 20.3033 mL | |
| 5 mM | 0.4061 mL | 2.0303 mL | 4.0607 mL | |
| 10 mM | 0.2030 mL | 1.0152 mL | 2.0303 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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