| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
NRF2[1]
The compound primarily targets the glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Its inhibition of PGK1 leads to the intracellular accumulation of the reactive metabolite methylglyoxal, which ultimately activates the NRF2 pathway and also inactivates the pro-inflammatory NF-kappaB pathway by crosslinking its protein components. |
|---|---|
| ln Vitro |
In epidermal keratinocytes and dermal fibroblasts, CBR-470-2 (1-10 μM; 24 h) raises transcript levels of the NRF2-responsive genes NQO1 and HMOX1[1].
In vitro, treatment with CBR-470-2 (1-10 microM for 24 hours) significantly increases the transcript levels of the canonical NRF2-responsive antioxidant genes NQO1 and HMOX1 in epidermal keratinocytes and dermal fibroblasts, confirming its on-target activity in primary human cells. |
| ln Vivo |
In vivo, CBR-470-2 (50 mg/kg; po twice daily for 10 d) causes NRF2 signaling to become activated[1].
In vivo, oral administration of CBR-470-2 (50 mg/kg, twice daily for 10 days) robustly induces the activation of NRF2 signaling in mice. In a UVB-induced skin damage model, this treatment resulted in a decrease in epidermal thickness and improved wound healing outcomes, demonstrating its beneficial effects in mitigating skin pathology. |
| Enzyme Assay |
Experiments often utilize purified phosphoglycerate kinase 1 (PGK1) and its substrates. The accumulation of the downstream metabolite methylglyoxal in the reaction mixture can be detected via mass spectrometry or a modified glyoxal-specific probe, providing a direct measure of the compound's target engagement.
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| Cell Assay |
Primary human cells, such as epidermal keratinocytes and dermal fibroblasts, are treated with CBR-470-2 at concentrations ranging from 1 to 10 microM for 24 hours. After treatment, cells are lysed and NRF2 target gene expression (NQO1 and HMOX1) is quantified by qPCR or NRF2 protein levels are assessed by Western blot to evaluate pathway activation.
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| Animal Protocol |
Animal/Disease Models: balb/c (Bagg ALBino) mouse (5-week old) are exposed to UVB[1] Dosage : 50 mg/kg
Route of Administration: Po twice (two times) daily for 10 days Experimental Results: Resulted in comparable beneficial effects on erythema histological scores and total wounded area. diminished epidermal thickness in response to UV exposure. The compound is typically administered orally to animal models, with a common dosing regimen being 50 mg/kg, twice daily. This regimen has been shown to induce NRF2 signaling in murine models, such as the 5-week-old Balb/c mouse model for UVB-induced skin damage. |
| ADME/Pharmacokinetics |
CBR-470-2 demonstrates favorable oral bioavailability and dose-dependent pharmacodynamic activity in mice. The compound is typically formulated in a vehicle such as 10% DMSO in corn oil for in vivo administration and is stable under proper storage conditions.
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| Toxicity/Toxicokinetics |
While CBR-470-2 is a valuable research tool and has shown good tolerability in short-term preclinical studies, specific toxicity data (e.g., LD50 values) are not publicly available. It is intended for research purposes only, and standard safety precautions for chemical handling should be practiced.
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| References | |
| Additional Infomation |
CBR-470-2 is used as a chemical probe to study the link between central carbon metabolism and the KEAP1-NRF2 signaling axis. It is also being used to explore the novel mechanism by which PGK1 inhibition can attenuate NF-kappaB signaling, highlighting its potential for investigating inflammatory diseases and therapeutic strategies to mitigate immune overactivation.
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| Molecular Formula |
C12H13CL2NO6S2
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|---|---|
| Molecular Weight |
402.27071928978
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| Exact Mass |
400.956
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| CAS # |
2416095-00-4
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| PubChem CID |
155819525
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| Appearance |
White to off-white solid powder
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| LogP |
-0.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
23
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| Complexity |
654
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| Defined Atom Stereocenter Count |
2
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| SMILES |
ClC1=C(C=CC(=C1)S([C@H]1CS(C[C@@H]1NCC(=O)O)(=O)=O)(=O)=O)Cl
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| InChi Key |
FNQDSYKGBCVHHI-QWRGUYRKSA-N
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| InChi Code |
InChI=1S/C12H13Cl2NO6S2/c13-8-2-1-7(3-9(8)14)23(20,21)11-6-22(18,19)5-10(11)15-4-12(16)17/h1-3,10-11,15H,4-6H2,(H,16,17)/t10-,11-/m0/s1
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| Chemical Name |
2-[[(3S,4R)-4-(3,4-dichlorophenyl)sulfonyl-1,1-dioxothiolan-3-yl]amino]acetic acid
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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 :~200 mg/mL (~497.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (12.43 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 50.0 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 | 2.4859 mL | 12.4295 mL | 24.8589 mL | |
| 5 mM | 0.4972 mL | 2.4859 mL | 4.9718 mL | |
| 10 mM | 0.2486 mL | 1.2429 mL | 2.4859 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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