| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
ERα ERβ
OP-1074 specifically targets Estrogen Receptor alpha (ERalpha) and Estrogen Receptor beta (ERbeta). It acts as a pure antagonist and promotes the degradation of the estrogen receptor, which is a key strategy for treating ER-positive breast cancer, particularly in cases that have developed resistance to conventional endocrine therapies. |
|---|---|
| ln Vitro |
OP-1074 (0-100 nM; 24 hours) suppresses MCF-7 cells and CAMA-1 cells proliferation with IC50 values of 6.3 and 9.2 nM, respectively[1]. OP-1074 (100 nM; 24 hours) destabilizatizes ERα protein expression in MCF-7 and CAMA-1 cells[1].
In cell-free biochemical assays, OP-1074 potently inhibits 17beta-estradiol (E2)-stimulated transcriptional activity with IC50 values of 1.6 nM and 3.2 nM for ERalpha and ERbeta, respectively.In cell-based assays, it effectively suppresses the proliferation of MCF-7 and CAMA-1 breast cancer cells with IC50 values of 6.3 nM and 9.2 nM, respectively, at 24 hours. |
| ln Vivo |
In a tamoxifen-resistant MCF7/HER2/neu xenograft model, OP-1074 demonstrated significantly greater tumor shrinkage compared to the clinically used SERD fulvestrant.In vivo, it acts as a pure antiestrogen completely lacking tissue-specific agonist activity, which is crucial for preventing and treating endocrine resistance in breast cancer.
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| Enzyme Assay |
Cell-free binding assays are performed using purified estrogen receptors (ERalpha and ERbeta). The compound is incubated with the receptor and a fluorescently labeled estrogen ligand. After reaching equilibrium, the IC50 is determined by measuring the decrease in fluorescence polarization or via a time-resolved fluorescence resonance energy transfer (TR-FRET) assay.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: MCF-7 cells, CAMA-1 cells Tested Concentrations: 0 nM, 10 nM,100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibited breast cancer cell proliferation. Western Blot Analysis[1] Cell Types: MCF-7 cells, CAMA-1 cells Tested Concentrations: 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Downregulated ERα protein expression. Cell-based assays are conducted in ER-positive breast cancer cell lines (e.g., MCF-7, CAMA-1). Cells are seeded in 96-well plates and treated with serial dilutions of OP-1074 for 24-72 hours. Cell proliferation is quantified using a standard Cell Counting Kit-8 (CCK-8) or a Resazurin-based assay to calculate the half-maximal inhibitory concentration (IC50). |
| Animal Protocol |
Female athymic nude mice bearing established tamoxifen-resistant MCF7/HER2/neu xenograft tumors are used. Mice are randomized into treatment groups and receive OP-1074 via subcutaneous injection or oral gavage. Tumor dimensions are measured twice weekly with calipers, and tumor volume is calculated. Efficacy is determined by comparing the tumor growth inhibition (TGI) rate to vehicle and fulvestrant control groups.
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| ADME/Pharmacokinetics |
OP-1074 is orally bioavailable and has improved pharmacokinetic properties over fulvestrant, which requires intramuscular administration. It is characterized by its ability to fully saturate and degrade ER in vivo, which addresses the poor PK properties of earlier SERDs that limited their therapeutic potential at standard doses.
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| Toxicity/Toxicokinetics |
In preclinical models, OP-1074 is well-tolerated at efficacious doses. Unlike selective estrogen receptor modulators (SERMs) like tamoxifen, which exhibit partial agonism in the uterus, OP-1074 acts as a pure antagonist in all tissues, thereby avoiding the risk of agonist-driven side effects and the development of resistance associated with partial agonism.
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| References | |
| Additional Infomation |
OP-1074 is a research compound that has been structurally analyzed to reveal the importance of a stereospecific methyl group on its pyrrolidine side chain for its pure antiestrogenic activity, particularly its effect on receptor helix 12.It is intended for research use only and has not been approved for clinical application.
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| Molecular Formula |
C29H31NO4
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|---|---|
| Molecular Weight |
457.560748338699
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| Exact Mass |
457.225
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| CAS # |
1443752-76-8
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| Related CAS # |
(R)-OP-1074;1443752-77-9
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| PubChem CID |
71580998
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| Appearance |
White to off-white solid powder
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| LogP |
5.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
694
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O(C1C=CC(=CC=1)[C@H]1C(C2C=CC(=CC=2)O)=C(C)C2C=CC(=CC=2O1)O)CCN1CC[C@@H](C)C1
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| InChi Key |
KDVXAPCZVZMPMU-XBBWARJSSA-N
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| InChi Code |
InChI=1S/C29H31NO4/c1-19-13-14-30(18-19)15-16-33-25-10-5-22(6-11-25)29-28(21-3-7-23(31)8-4-21)20(2)26-12-9-24(32)17-27(26)34-29/h3-12,17,19,29,31-32H,13-16,18H2,1-2H3/t19-,29+/m1/s1
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| Chemical Name |
(2S)-3-(4-hydroxyphenyl)-4-methyl-2-[4-[2-[(3R)-3-methylpyrrolidin-1-yl]ethoxy]phenyl]-2H-chromen-7-ol
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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: 100 mg/mL (218.55 mM)
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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 | 2.1855 mL | 10.9275 mL | 21.8551 mL | |
| 5 mM | 0.4371 mL | 2.1855 mL | 4.3710 mL | |
| 10 mM | 0.2186 mL | 1.0928 mL | 2.1855 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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