| Size | Price | Stock | Qty |
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| 25mg |
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Purity: ≥98%
PDM-2 (PDM2), a trans-resveratrol analog, is a novel selective, high-affinity aryl hydrocarbon receptor (AhR) antagonist with an Ki of 1.2±0.4 nM. This study investigated the in vitro protective effects of three derivatives of resveratrol, i.e., piceatannol, PDM2 and PDM11, compared with resveratrol as reference compound, against oxidation of linoleate micelles (10(-2)M) initiated by radiolysis-generated hydroxyl radicals. Lipid peroxidation was monitored by conjugated dienes (differential absorbance at 234nm), and by hydroperoxides (reverse phase HPLC with chemiluminescence detection). The higher the concentration of resveratrol or piceatannol (from 10(-5)M to 10(-4)M), the stronger the antioxidant ability. Piceatannol, with the presence of an additional hydroxyl group, showed a better antioxidant effect than resveratrol for a given concentration (competition with the fatty acid to scavenge lipid peroxyl radicals LOO), whereas PDM2 and PDM11, without any hydroxyl group, did not exhibit any significant protective effect. A lower limit for the LOO rate constant has been estimated for piceatannol (>/=1.4x10(5)M(-1)s(-1)) and for resveratrol (>/=0.3x10(5)M(-1)s(-1)).
| Targets |
PDM2 (compound 4b) shows no affinity for the estrogen receptor (ER) and a Ki value of 1.2±0.4 nM for AhR, confirming that substituting chlorine for the hydroxyl group will prevent binding to the ER and greatly boost the affinity for AhR [1].
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| ln Vitro |
PDM2 (compound 4b) shows no affinity for the estrogen receptor (ER) and a Ki value of 1.2±0.4 nM for AhR, confirming that substituting chlorine for the hydroxyl group will prevent binding to the ER and greatly boost the affinity for AhR [1].
Compound 4b and 4j acted as potent antagonists of the AhR, completely suppressing TCDD (5 nM)-stimulated CAT reporter gene transcription in 47DRE cells at 10 µM, and were about 10-fold more efficient than resveratrol. Compound 4i, despite having the highest affinity for AhR (Ki = 0.2 nM), behaved as an agonist, stimulating AhR-mediated transcription in the 47DRE reporter cell line. Compounds 4b, 4i, and 4j, which lacked measurable affinity for ER, showed no effect on ER-driven luciferase reporter transcription in MELN cells, confirming their selectivity for AhR over ER. Resveratrol and its halogenated derivatives (like 4b) showed no cytotoxicity up to 10 µM in various human tumor cell lines (A549, MCF-7, T47D). However, methoxy-substituted stilbenes (e.g., 4a, 5b) induced cytotoxicity at doses lower than 100 nM. [1] |
| Enzyme Assay |
AhR binding affinity was determined using a competitive radioligand binding assay. Cytosols from rabbit liver were incubated with 0.2 nM [³H]-TCDD and 12 concentrations of unlabeled test ligands ranging from 0.1 nM to 1 µM. IC₅₀ values were determined using curve-fitting software and converted to apparent inhibition constants (Ki) using the Cheng-Prusoff equation, assuming a Kd of 0.01 nM for TCDD.
ER binding affinity was measured similarly. Cytosols from MCF-7 cells (expressing ERα) were incubated with 2 nM [³H]-estradiol and eight concentrations of unlabeled test ligands ranging from 10 nM to 10 µM. IC₅₀ and Ki were calculated as above, assuming a Kd of 0.1 nM for estradiol. [1] |
| Cell Assay |
AhR-mediated transcriptional activity (agonist/antagonist properties) was assessed using a stable reporter cell line (47DRE) containing a DRE-TK-CAT construct. Cells were treated for 48 hours with either vehicle, various concentrations of test compounds alone, or test compounds in the presence of 5 nM TCDD. CAT expression was then analyzed. An agonist was defined as a compound stimulating CAT transcription, while an antagonist was defined as a compound capable of suppressing at least 50% of the TCDD-stimulated CAT activity.
ER-mediated transcriptional activity was measured using the MELN reporter cell line (containing an estrogen-responsive luciferase construct). Cells were incubated for 8 hours with vehicle, test compounds alone, or test compounds in the presence of 1 nM 17β-estradiol, followed by luciferase activity measurement. Definitions for agonist/antagonist were analogous to the AhR assay. Cytotoxicity was evaluated on human tumor cell lines A549 (lung carcinoma), MCF-7, and T47D (breast cancers). Toxicity was assessed after exposure to the compounds, though the specific assay method (e.g., MTT, cell counting) and exposure duration were not detailed in the provided text. [1] |
| Toxicity/Toxicokinetics |
In vitro cytotoxicity assays on human tumor cell lines (A549, MCF-7, T47D) showed that resveratrol and its halogenated homologues (e.g., compound 4b) were non-toxic at concentrations up to 10 µM. Conversely, methoxylated stilbene compounds, such as trimethoxy derivatives (4a, 5b) and 3,5-dimethoxy derivatives (4g, 5g), induced cytotoxicity at doses below 100 nM. Other 3,5-dimethoxy derivatives (4f, 5f, 4h, 5h) showed cytotoxicity only at concentrations above 10 µM. [1]
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| References | |
| Additional Infomation |
These stilbene derivatives were designed as isosteric modifiers of resveratrol to develop high-affinity and selective AhR modulators while eliminating their affinity for ER. Compounds 4b and 4j were identified as selective high-affinity AhR antagonists (Ki values in the low nM range) and showed no detectable affinity for ER, making them potential lead compounds for developing pure AhR antagonists. Compound 4i was identified as a selective high-affinity AhR agonist (Ki = 0.2 nM) and showed no detectable affinity for ER. The absence of the phenolic hydroxyl group in these compounds (replaced by halogens or other groups) inhibits their antioxidant properties and binding to ER, potentially eliminating estrogen-related risks (e.g., increased cancer risk). Antagonist compounds (4b, 4j) are considered to have potential application value as a non-hormonal bone protection therapy by inhibiting the expression of AhR-dependent interleukins in bone tissue. [1]
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| Molecular Formula |
C14H9CL3
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| Molecular Weight |
283.58000
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| Exact Mass |
281.98
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| Elemental Analysis |
C, 59.30; H, 3.20; Cl, 37.50
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| CAS # |
688348-25-6
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| Related CAS # |
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| PubChem CID |
9838722
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
394.2±42.0 °C at 760 mmHg
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| Flash Point |
276.5±23.5 °C
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| Vapour Pressure |
0.0±0.9 mmHg at 25°C
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| Index of Refraction |
1.675
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| LogP |
6.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
0
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
246
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC=C1/C=C/C2=CC(=CC(=C2)Cl)Cl)Cl
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| InChi Key |
JMYNPQVCVQVODQ-OWOJBTEDSA-N
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| InChi Code |
InChI=1S/C14H9Cl3/c15-12-5-3-10(4-6-12)1-2-11-7-13(16)9-14(17)8-11/h1-9H/b2-1+
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| Chemical Name |
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.82 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 25.0 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 | 3.5263 mL | 17.6317 mL | 35.2634 mL | |
| 5 mM | 0.7053 mL | 3.5263 mL | 7.0527 mL | |
| 10 mM | 0.3526 mL | 1.7632 mL | 3.5263 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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