| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
ERα 9.0 nM (Ki) ERβ 3.6 nM (Ki)
(R,R)-THC targets the estrogen receptor (ER) subtypes, specifically ERalpha and ERbeta. It acts as an agonist (activator) of the ERalpha receptor and as an antagonist (inhibitor) of the ERbeta receptor. The estrogen receptors are ligand-activated transcription factors belonging to the nuclear receptor superfamily. They play crucial roles in regulating gene expression related to reproductive development, metabolic homeostasis, and cell proliferation. By differentially modulating the two ER subtypes, (R,R)-THC can influence these signaling pathways. |
|---|---|
| ln Vitro |
In cell-free in vitro assays, (R,R)-THC demonstrates potent and differential binding affinity for estrogen receptor subtypes. It exhibits Ki values of 9.0 nM for ERalpha and 3.6 nM for ERbeta, indicating a higher binding affinity for the ERbeta subtype. The relative binding affinity (RBA) values for ERbeta and ERalpha are reported as 25 and 3.6, respectively. These data confirm its role as a potent ERalpha agonist and ERbeta antagonist, although the specific functional activities (agonism/antagonism) are defined in cell-based assays rather than cell-free binding studies. In vitro cell-based studies have defined the functional activity of (R,R)-THC as an ERalpha agonist and an ERbeta antagonist. This means that in cells expressing ERalpha, the compound activates estrogen-responsive gene transcription, while in cells expressing ERbeta, it blocks the transcriptional activity typically induced by natural estrogens. Specific cellular efficacy endpoints, such as EC50 values for ERalpha activation or IC50 values for ERbeta antagonism, are not standardly reported in supplier data sheets. Its differential activity on the two ER subtypes makes it a valuable tool for studying subtype-specific estrogen signaling.
|
| ln Vivo |
No dedicated in vivo (animal) pharmacological activity studies for (R,R)-THC alone are available in standard product documentation. Since it is not a drug candidate, standard animal efficacy studies (e.g., xenograft tumor models, metabolic disease models) have not been performed. However, the unlabeled parent compound or related ER modulators are used in animal models for studying estrogen receptor biology. For any such application, (R,R)-THC would be formulated in solvents like DMSO, ethanol, or PEG400 and administered via intraperitoneal injection or oral gavage.
|
| Enzyme Assay |
For in vitro ER competition binding assays, a typical protocol: Recombinant human ERalpha or ERbeta protein is incubated with 0.5-2 nM [3H]-estradiol in assay buffer (50 mM Tris-HCl, pH 7.5, 1 mM EDTA, 10% glycerol, 0.1% BSA) at 4degC for 12-16 hours. Increasing concentrations of (R,R)-THC (0.1 nM to 10 uM) are added to compete for binding. Non-specific binding is determined in the presence of 500-fold excess unlabeled estradiol. Bound and free radioligand are separated by dextran-coated charcoal or filtration, and bound radioactivity is counted. Ki values are calculated using the Cheng-Prusoff equation.
|
| Cell Assay |
For cell-based functional assays: ER-positive cells (e.g., MCF-7 cells for ERalpha, or HEK293 cells transfected with ERbeta and an estrogen-responsive luciferase reporter gene) are seeded in 96-well plates. After 24 hours, cells are treated with varying concentrations of (R,R)-THC (0.1 nM to 10 uM) for 24-48 hours. For antagonism assays, cells are co-treated with 1 nM estradiol (E2). After incubation, cells are lysed, and luciferase activity (or other reporter) is measured. EC50 for ERalpha agonism and IC50 for ERbeta antagonism are calculated. Cell viability is assessed by MTT or CCK-8 assay to ensure observed effects are not due to cytotoxicity.
|
| Animal Protocol |
No dedicated animal study protocols exist for (R,R)-THC alone. If applied in vivo, a typical protocol for estrogen receptor modulator studies: 6-8 week old female ovariectomized mice/rats are used to eliminate endogenous estrogen. (R,R)-THC is formulated in a vehicle such as 10% DMSO, 10% Tween 80, and 80% saline, or 5% ethanol in corn oil. The compound is administered by intraperitoneal injection or oral gavage at doses ranging from 1 to 50 mg/kg daily for 1-4 weeks. Animals are monitored for body weight, uterine weight (to assess estrogenic activity), and other tissue-specific endpoints. At study termination, blood and target tissues are collected for analysis of gene expression, protein levels, and histology.
|
| ADME/Pharmacokinetics |
No specific pharmacokinetic (PK) data for (R,R)-THC have been reported, as it is a research tool compound and not a drug candidate. Based on its chemical properties (logP = 5.173, molecular weight = 320.42), it is highly lipophilic, suggesting good membrane permeability and potential for high plasma protein binding (>95%). After oral administration, it would likely be absorbed slowly, with a Tmax of 2-6 hours. The compound would be distributed to lipid-rich tissues (adipose, liver, brain). Metabolism is expected to occur via cytochrome P450 enzymes (primarily CYP3A4 and CYP2C subfamilies), including hydroxylation of the ethyl groups or aromatic rings, followed by glucuronidation or sulfation. The elimination half-life is not known but is expected to be moderate (4-12 hours) in rodents.
|
| Toxicity/Toxicokinetics |
No dedicated toxicology data for (R,R)-THC are available. As an estrogen receptor modulator, it may carry class-related risks. Potential adverse effects include: (1) estrogenic effects such as uterine stimulation (due to ERalpha agonism), causing endometrial thickening or vaginal cornification; (2) anti-estrogenic effects in ERbeta-expressing tissues (e.g., ovary, prostate, colon); (3) hepatotoxicity (cholestasis, elevated liver enzymes) as seen with some synthetic ER modulators; (4) thrombotic risk (hypercoagulability) due to changes in coagulation factor synthesis. Standard safety precautions: wear PPE (gloves, lab coat, safety goggles). Avoid inhalation and skin contact. Since it is a synthetic ER modulator, female personnel should handle with caution. Not for human or veterinary use.
|
| References | |
| Additional Infomation |
(R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-dylodiol is a carbon-tetracyclic compound formed by the substitution of hydroxyl groups at the 2 and 8 positions and ethyl groups at the 5 and 11 positions (5R,11R- stereoisomer). It is an agonist of estrogen receptor α (ER-α) and an antagonist of estrogen receptor β (ER-β). It possesses the functions of an estrogen receptor antagonist, estrogen receptor agonist, anti-aging agent, and neuroprotective agent. It is a carbon-tetracyclic compound and also a polyphenol.
(R,R)-THC is a research-use only compound, not approved for diagnostic or therapeutic use. It has not been evaluated in clinical trials. Its primary application is as a chemical probe to study estrogen receptor subtype-specific signaling. It serves as an ERalpha-selective agonist and an ERbeta antagonist, useful for dissecting the distinct biological roles of ERalpha vs. ERbeta in various tissues and disease states. The mechanism of action involves binding to the ligand-binding domain of ERalpha and ERbeta, inducing conformational changes that lead to differential recruitment of coactivators/corepressors and subsequent activation or repression of target gene transcription. No functional data is available for typical pharmacology of this compound. (R,R)-THC should be stored at -20degC, protected from light and moisture, and is stable for up to 3 years as a powder. |
| Molecular Formula |
C22H24O2
|
|---|---|
| Molecular Weight |
320.42
|
| Exact Mass |
320.178
|
| CAS # |
221368-54-3
|
| PubChem CID |
446849
|
| Appearance |
Solid powder
|
| LogP |
5.173
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
24
|
| Complexity |
452
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CC[C@@H]1CC2C=C(C=CC=2C2[C@@H](CC3C=C(O)C=CC=3C1=2)CC)O
|
| InChi Key |
MASYAWHPJCQLSW-ZIAGYGMSSA-N
|
| InChi Code |
InChI=1S/C22H24O2/c1-3-13-9-15-11-17(23)6-8-20(15)22-14(4-2)10-16-12-18(24)5-7-19(16)21(13)22/h5-8,11-14,23-24H,3-4,9-10H2,1-2H3/t13-,14-/m1/s1
|
| Chemical Name |
(5R,11R)-5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8-diol
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| 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
|
|---|---|
| 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 | 3.1209 mL | 15.6045 mL | 31.2090 mL | |
| 5 mM | 0.6242 mL | 3.1209 mL | 6.2418 mL | |
| 10 mM | 0.3121 mL | 1.5605 mL | 3.1209 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
