| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg | |||
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| 100mg | |||
| Other Sizes |
| Targets |
Keap1-Nrf2[2]
CBR-470-1 directly targets and inhibits phosphoglycerate kinase 1 (PGK1). Inhibition of PGK1 leads to the accumulation of methylglyoxal (MGO), which in turn inactivates KEAP1 (the negative regulator of NRF2). This results in NRF2 stabilization and nuclear translocation, upregulating antioxidant response element (ARE)-driven genes. |
|---|---|
| ln Vitro |
In the ARE-LUC reporter assay using IMR32 cells, CBR-470-1 (0.01-10 μM; 24 h) shows an EC50 of 962 nM[1]. Nrf2 protein accumulates in IMR32 cells in a dose- and time-dependent manner when exposed to CBR-470-1 (0.5–20 μM; 1–24 h)[1]. The Nrf2 signaling cascade in SH-SY5Y cells is activated by CBR-470-1 (10 μM; 4 h)[2]. In SH-SY5Y neural cells, CBR-470-1 (10 μM; 2 h) reduces MPP+-induced oxidative injury[2].
In vitro, CBR-470-1 activates NRF2 signaling with an EC₅0 of approximately 1 uM in cellular ARE-luciferase assays. It induces transcript levels of NQO1 and HMOX1, enhances NRF2 protein stabilization, and protects SH-SY5Y neuronal cells from MPP+-induced cytotoxicity in a NRF2-dependent manner. |
| ln Vivo |
In vivo, CBR-470-1 has been shown to be efficacious in a NRF2-dependent mouse model of UV-induced skin damage. It demonstrates the physiological relevance of activating KEAP1-NRF2 signaling via PGK1 inhibition. Its efficacy is dependent on the presence of a functional NRF2 pathway.
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| Enzyme Assay |
A non-cell assay would involve assessing PGK1 activity directly: incubating recombinant PGK1 with 3-phosphoglycerate (3-PG) and ATP, and measuring the production of 1,3-bisphosphoglycerate (1,3-BPG) and ADP. CBR-470-1 is added to the reaction, and enzyme activity is measured by coupled enzyme assay (using GAPDH) or by direct LC-MS detection of metabolites.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: IMR32 cells Tested Concentrations: 0.5, 1, 5, 10, 20 μM Incubation Duration: 1, 2, 4, 8, 24 h Experimental Results: Increased the Nrf2 protein in a dose- and time-dependent manner. Increased both mRNA and protein levels of the Nrf2-responsive genes NQO1 and HMOX1. SH-SY5Y neuroblastoma cells (differentiated or undifferentiated) are treated with CBR-470-1 (10 microM) for 4-24 hours. ARE-luciferase reporter activity is measured. NRF2 translocation is assessed by immunofluorescence or subcellular fractionation followed by Western blot. Target gene expression (NQO1, HMOX1) is measured by qPCR. |
| Animal Protocol |
Animal studies are conducted in mice. CBR-470-1 is administered topically (for skin models) or systemically (intraperitoneal injection). In the UV-damage mouse model, skin is exposed to UVB radiation after treatment, and the extent of skin damage and inflammation is assessed histologically.
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| ADME/Pharmacokinetics |
Limited PK data available from preclinical studies. The compound inhibits PGK1, a metabolic enzyme, suggesting potential for cellular accumulation. The methylglyoxal-mediated mechanism of action implies that the compound's effects may be sustained even after compound clearance due to persistent KEAP1 modification.
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| Toxicity/Toxicokinetics |
Toxicity data from in vivo studies indicate that CBR-470-1 is well-tolerated at the doses used (e.g., topical application for UV damage studies). The LD₅0 and detailed safety profile have not been fully established in published literature. Standard laboratory safety precautions apply.
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| References | |
| Additional Infomation |
CBR-470-1 is a research tool for studying the KEAP1-NRF2 antioxidant pathway via metabolic regulation (PGK1 inhibition). Its unique mechanism of action-activating NRF2 through metabolite accumulation rather than direct KEAP1 binding-offers a distinct pharmacological strategy. It is not an approved drug.
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| Molecular Formula |
C14H20CLNO4S2
|
|---|---|
| Molecular Weight |
365.895900726318
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| Exact Mass |
365.052
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| CAS # |
2416095-06-0
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| PubChem CID |
20898025
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| Appearance |
White to yellow solid powder
|
| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
22
|
| Complexity |
569
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
ClC1C=CC(=CC=1)S([C@H]1CS(C[C@@H]1NCC(C)C)(=O)=O)(=O)=O
|
| InChi Key |
NFEQFEDSWINARK-KBPBESRZSA-N
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| InChi Code |
InChI=1S/C14H20ClNO4S2/c1-10(2)7-16-13-8-21(17,18)9-14(13)22(19,20)12-5-3-11(15)4-6-12/h3-6,10,13-14,16H,7-9H2,1-2H3/t13-,14-/m0/s1
|
| Chemical Name |
(3S,4R)-4-(4-chlorophenyl)sulfonyl-N-(2-methylpropyl)-1,1-dioxothiolan-3-amine
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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 :~200 mg/mL (~546.60 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.66 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 (13.66 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (13.66 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7330 mL | 13.6649 mL | 27.3299 mL | |
| 5 mM | 0.5466 mL | 2.7330 mL | 5.4660 mL | |
| 10 mM | 0.2733 mL | 1.3665 mL | 2.7330 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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