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| Targets |
PROTAC ERalpha Degrader-2 targets estrogen receptor alpha (ERalpha), a nuclear receptor that plays a critical role in the growth and progression of ER-positive breast cancers. ERalpha is a transcription factor that is activated by estrogen binding and regulates the expression of genes involved in cell proliferation and survival. The compound uses PROTAC technology to recruit ERalpha to an E3 ubiquitin ligase (cIAP1), inducing its ubiquitination and subsequent proteasomal degradation. The compound consists of an ERalpha ligand derived from a non-steroidal estrogen analog, a linker, and a ligand that binds to the cIAP1 E3 ligase. By degrading ERalpha, the compound reduces ERalpha levels and inhibits related signaling pathways.
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| ln Vitro |
PROTAC ERalpha Degrader-2 demonstrates potent in vitro activity in degrading ERalpha. In MCF7 human mammary tumor cells, the compound reduces ERalpha levels, reaching maximum degradation at a concentration of 30 microM. The compound's activity is concentration-dependent, with degradation observed at appropriate concentrations. As a PROTAC, the compound induces the ubiquitination and degradation of ERalpha through the recruitment of the cIAP1 E3 ubiquitin ligase. The compound's ability to degrade ERalpha makes it a valuable tool for studying ERalpha biology and evaluating ERalpha degradation as a therapeutic strategy for ER-positive breast cancer. Comprehensive in vitro activity data are available from research publications.
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| ln Vivo |
In vivo activity of PROTAC ERalpha Degrader-2 has not been extensively characterized in the public domain. As an ERalpha degrader, the compound would be expected to have antitumor activity in ER-positive breast cancer models. PROTACs that degrade ERalpha have been studied in various animal models of breast cancer. However, comprehensive in vivo efficacy studies using PROTAC ERalpha Degrader-2 specifically have not been widely published. The compound is primarily used as a research tool for in vitro studies of ERalpha degradation. Further research is needed to determine the in vivo activity of this compound.
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| Cell Assay |
In vitro cellular assays for PROTAC ERalpha Degrader-2 are performed using ERalpha-positive breast cancer cell lines such as MCF7. Cells are treated with varying concentrations of the compound for defined time periods (typically 24-72 hours). ERalpha protein levels are assessed by Western blot using ERalpha-specific antibodies. Maximum degradation is observed at 30 microM. ERalpha target gene expression (e.g., pS2, cyclin D1, c-Myc) is measured by qRT-PCR. Cell proliferation and viability are assessed using MTT or CellTiter-Glo assays. Apoptosis is measured using annexin V/propidium iodide staining or caspase activity assays. Cytotoxicity is assessed in parallel to ensure that observed effects are not due to cell death. Degradation efficacy is expressed as percent reduction in ERalpha levels compared to vehicle-treated controls.
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| Animal Protocol |
In vivo animal studies for PROTAC ERalpha Degrader-2 have not been extensively reported in the public domain. As an ERalpha degrader, the compound could potentially be evaluated in mouse xenograft models of ER-positive breast cancer. In such studies, the compound would be administered via intraperitoneal injection or oral gavage, and endpoints would include tumor growth, ERalpha degradation in tumor tissues, and biomarker analysis. However, comprehensive in vivo efficacy studies have not been widely published. The compound is primarily used as a research tool for in vitro studies.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of PROTAC ERalpha Degrader-2 have not been extensively characterized in the public domain. The compound has a molecular formula of C42H61N5O8 and a molecular weight of 763.96 g/mol. As a PROTAC with a relatively large molecular weight, the compound would be expected to have limited oral bioavailability and may be administered by injection. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and bioavailability have not been reported.
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| Toxicity/Toxicokinetics |
PROTAC ERalpha Degrader-2 is intended for laboratory research use only and has not undergone comprehensive toxicology testing. As a compound that induces protein degradation, the compound would be expected to have effects on ERalpha signaling and cell proliferation. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals would be monitored for signs of toxicity if the compound were to be evaluated in animal studies. Comprehensive toxicological characterization including genotoxicity and repeated-dose toxicity studies has not been reported. The compound is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
PROTAC ERalpha Degrader-2 is a PROTAC that degrades estrogen receptor alpha (ERalpha) by recruiting cIAP1 E3 ligase. It achieves maximum ERalpha degradation at 30 microM in MCF7 cells. The compound has a molecular formula of C42H61N5O8 and a molecular weight of 763.96 g/mol. PROTAC ERalpha Degrader-2 has not entered clinical trials and is available for research purposes only.
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| Molecular Formula |
C42H61N5O8
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|---|---|
| Molecular Weight |
763.962451696396
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| Exact Mass |
763.452
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| CAS # |
1351169-29-3
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| PubChem CID |
54764406
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| Appearance |
White to off-white solid powder
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
20
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| Heavy Atom Count |
55
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| Complexity |
1260
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| Defined Atom Stereocenter Count |
7
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| SMILES |
O(CC(NCCOCCOCCNC([C@H](CC(C)C)NC([C@H]([C@@H](CC1C=CC=CC=1)N)O)=O)=O)=O)/N=C1\CC[C@H]2[C@@H]3CCC4C=C(C=CC=4[C@H]3CC[C@@]2\1C)O
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| InChi Key |
MMDOSMHAAYKBET-UTCZBAMKSA-N
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| InChi Code |
InChI=1S/C42H61N5O8/c1-27(2)23-36(46-41(52)39(50)35(43)24-28-7-5-4-6-8-28)40(51)45-18-20-54-22-21-53-19-17-44-38(49)26-55-47-37-14-13-34-33-11-9-29-25-30(48)10-12-31(29)32(33)15-16-42(34,37)3/h4-8,10,12,25,27,32-36,39,48,50H,9,11,13-24,26,43H2,1-3H3,(H,44,49)(H,45,51)(H,46,52)/b47-37+/t32-,33-,34+,35-,36+,39+,42+/m1/s1
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| Chemical Name |
(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-N-[2-[2-[2-[[2-[(E)-[(8R,9S,13S,14S)-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ylidene]amino]oxyacetyl]amino]ethoxy]ethoxy]ethyl]-4-methylpentanamide
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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. |
| 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) |
DMSO : ~200 mg/mL (~261.79 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (6.54 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3090 mL | 6.5448 mL | 13.0897 mL | |
| 5 mM | 0.2618 mL | 1.3090 mL | 2.6179 mL | |
| 10 mM | 0.1309 mL | 0.6545 mL | 1.3090 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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