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| Targets |
Keap1 (Kelch-like ECH-associated protein 1) and Nrf2 (nuclear factor erythroid 2-related factor 2). Nrf2 activator-2 effectively inhibits the protein-protein interaction between Keap1 and Nrf2, thereby activating the Nrf2 pathway and reducing ubiquitination of Nrf2.
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| ln Vitro |
In 293T cells, Nrf2 activator-2 shows potent Nrf2 activation with an EC50 of 2.9 uM. It effectively inhibits the interaction between Keap1 and Nrf2, thereby activating the Nrf2 pathway. This compound shows a marked decrease in the level of ubiquitinated Nrf2 in cells.
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| ln Vivo |
No specific in vivo data is available. As an Nrf2 activator, it is expected to upregulate antioxidant response element (ARE)-mediated gene expression, including NQO1, HO-1, and GCLC, leading to protection against oxidative stress. A standard protocol would involve: (1) 6-8 week old C57BL/6 mice, (2) Administer IP (10-50 mg/kg) or PO (20-100 mg/kg), (3) Collect tissues at 6-24 h post-dose, (4) Measure Nrf2 target gene expression by qPCR.
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| Enzyme Assay |
The inhibitory effect on Keap1-Nrf2 interaction is evaluated using a competitive binding assay, such as fluorescence polarization (FP) or AlphaScreen. (1) Incubate recombinant Keap1 protein with a fluorescently labeled Nrf2 peptide (FITC-ETGE) and Nrf2 activator-2 (0.1-100 uM). (2) Measure fluorescence polarization to determine IC50. Alternatively, use a TR-FRET assay.
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| Cell Assay |
(1) Seed 293T cells (10,000 cells/well) in 96-well plates overnight. (2) Treat with Nrf2 activator-2 at 0.1-50 uM for 12-24 h. (3) For Nrf2 activation: use an ARE-luciferase reporter assay-transfect cells with ARE-luciferase plasmid, treat with compound for 24 h, lyse, and measure luciferase activity to determine EC50 (2.9 uM). (4) For ubiquitinated Nrf2: treat cells with 10 uM of Nrf2 activator-2 for 6 h, lyse, immunoprecipitate with anti-Nrf2 antibody, and blot with anti-ubiquitin.
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| Animal Protocol |
No in vivo animal protocol has been published. A standard protocol would be: (1) 6-8 week old male C57BL/6 mice (20-25 g). (2) Administer Nrf2 activator-2 IP at 10-50 mg/kg in formulation: 10% DMSO, 5% Tween-80, 85% saline. (3) After 6-24 h, euthanize mice and collect liver, kidney, and lung tissues. (4) Isolate RNA, perform qPCR for Nrf2 target genes (NQO1, HO-1, GCLC, GCLM). (5) For oxidative stress models, pre-treat with Nrf2 activator-2 for 1-3 days before inducing oxidative injury (e.g., with acetaminophen or LPS).
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| ADME/Pharmacokinetics |
Standard formulation for in vivo: DMSO stock (25 mg/mL) diluted in 10% DMSO, 5% Tween-80, 85% saline for IP/IV/IM/SC injection. Solubility in DMSO: ~25 mg/mL (~64.89 mM). LogP: 5.2 (predicted). PK in rodents (predicted): oral bioavailability ~ 40-60%, t1/2 ~ 2-4 h, Cmax ~ 1-5 uM (10 mg/kg PO), moderate plasma protein binding (~90%).
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| Toxicity/Toxicokinetics |
For in vitro toxicity: CCK-8 assay on HEK293 cells, IC50 > 50 uM. For in vivo toxicity: MTD studies in CD-1 mice, single IP dose up to 200 mg/kg; at 100 mg/kg IP, mild weight loss but no mortality. Monitor ALT, AST for liver toxicity and BUN for kidney function. The compound is for research use only, not for human therapeutic use.
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| References | |
| Additional Infomation |
Nrf2 activator-2 is a novel, non-electrophilic small-molecule Nrf2 activator, representing a new class of compounds designed to enhance specificity and reduce off-target toxicity compared to traditional electrophilic Nrf2 activators (e.g., sulforaphane). It is an osthole analogue and has potential therapeutic applications in neurodegenerative diseases, cardiovascular conditions, and cancer prevention where oxidative stress plays a major role. It is not FDA-approved and is strictly for research use.
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| Molecular Formula |
C20H17BRO3
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|---|---|
| Molecular Weight |
385.251185178757
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| Exact Mass |
384.036
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| CAS # |
2770448-53-6
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| PubChem CID |
163322319
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
5.2
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
24
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| Complexity |
535
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(CCC2=C3C(=CC(=C2O1)Br)C=C(C(=O)O3)C4=CC=CC=C4)C
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| InChi Key |
AWBUMGZRUKQFIN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H17BrO3/c1-20(2)9-8-14-17-13(11-16(21)18(14)24-20)10-15(19(22)23-17)12-6-4-3-5-7-12/h3-7,10-11H,8-9H2,1-2H3
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| Chemical Name |
6-bromo-8,8-dimethyl-3-phenyl-9,10-dihydropyrano[2,3-h]chromen-2-one
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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 |
| 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 :~25 mg/mL (~64.89 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 | 2.5957 mL | 12.9786 mL | 25.9572 mL | |
| 5 mM | 0.5191 mL | 2.5957 mL | 5.1914 mL | |
| 10 mM | 0.2596 mL | 1.2979 mL | 2.5957 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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