| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
GSK3β 1.05 μM (IC50) GSK3α 6.7 μM (IC50)
GSK3 (glycogen synthase kinase 3). (R)-BRD3731 is a GSK3 inhibitor with IC50 values of 1.05 microM for GSK3beta and 6.7 microM for GSK3alpha, showing significantly lower potency compared to its (S)-enantiomer (BRD3731, with IC50 values of 15 nM for GSK3beta and 215 nM for GSK3alpha). |
|---|---|
| ln Vitro |
(R)-BRD3731 inhibits GSK3beta with an IC50 of 1.05 microM and GSK3alpha with an IC50 of 6.7 microM. These values are approximately 70-fold and 31-fold higher, respectively, than those of the (S)-enantiomer, indicating that the (S)-configuration is critical for high-affinity binding and potent inhibition. No additional in vitro activity data are reported.
|
| ln Vivo |
No specific in vivo activity data are reported for (R)-BRD3731. Given its substantially lower potency against GSK3 compared to BRD3731, it is not expected to exhibit significant in vivo efficacy at comparable doses. It may serve as a negative control in GSK3-targeting pharmacological studies to confirm that observed effects are due to GSK3 inhibition.
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| Enzyme Assay |
Cell-free GSK3beta and GSK3alpha activity assays are performed as described for BRD3731. Recombinant human GSK3 enzymes are incubated with a biotinylated peptide substrate and ATP in the presence of increasing concentrations of (R)-BRD3731 (0.001-1000 uM) in assay buffer (50 mM HEPES, pH 7.4, 10 mM MgCl2). After incubation, the phosphorylated product is detected by TR-FRET using a terbium-labeled phospho-specific antibody. IC50 values are determined by nonlinear regression.
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| Cell Assay |
Cell-based assays are typically performed using SH-SY5Y cells treated with (R)-BRD3731 (0.1-100 uM) for 24 hours. Western blot analysis of cell lysates is used to assess the phosphorylation status of GSK3beta downstream targets such as CRMP2 or beta-catenin. The (R)-enantiomer may show minimal effects at concentrations where BRD3731 is highly active, confirming its lower potency.
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| Animal Protocol |
No in vivo animal protocols are published for (R)-BRD3731. If used as a negative control in vivo, it would be administered to rodents by oral gavage or intraperitoneal injection at doses comparable to those used for BRD3731. Blood and brain tissue would be collected for PK/PD analysis. Efficacy would be assessed in relevant disease models, but such studies are not reported.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for (R)-BRD3731. It has a molecular weight of 377.52, identical to that of BRD3731. The chemical name is (4R)-3-(2,2-dimethylpropyl)-4,7,7-trimethyl-4-phenyl-2H,4H,5H,6H,7H,8H,9H-pyrazolo[3,4-b]quinolin-5-one. Density: 1.2+/-0.1 g/cm3, boiling point: 502.2+/-60.0 degC. DMSO solubility is expected to be similar to BRD3731 (≈50 mg/mL).
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for (R)-BRD3731. As it is chemically similar to BRD3731 but with lower potency, its toxicity profile is expected to be less pronounced at equivalent doses. Standard toxicological assessments (hERG, Ames, acute toxicity) have not been performed. No clinical trials have been conducted.
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| References | |
| Additional Infomation |
Other information: (R)-BRD3731 is a research-grade chemical (CAS# 2056262-08-7) with purity ≥98%. It is not FDA-approved. The compound is useful for SAR studies of GSK3 inhibitors, as it represents the less active enantiomer, allowing researchers to confirm that biological effects are due to GSK3 inhibition rather than off-target effects. It is for research use only.
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| Molecular Formula |
C24H31N3O
|
|---|---|
| Molecular Weight |
377.52244591713
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| Exact Mass |
377.246
|
| CAS # |
2056262-08-7
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| Related CAS # |
BRD3731;2056262-07-6
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| PubChem CID |
154828619
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| Appearance |
Light yellow to yellow solid powder
|
| LogP |
5.6
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
28
|
| Complexity |
668
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
O=C1CC(C)(C)CC2=C1[C@](C)(C1C=CC=CC=1)C1=C(CC(C)(C)C)NN=C1N2
|
| InChi Key |
YZRXTIGAQRIAEX-DEOSSOPVSA-N
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| InChi Code |
InChI=1S/C24H31N3O/c1-22(2,3)12-17-20-21(27-26-17)25-16-13-23(4,5)14-18(28)19(16)24(20,6)15-10-8-7-9-11-15/h7-11H,12-14H2,1-6H3,(H2,25,26,27)/t24-/m0/s1
|
| Chemical Name |
(4R)-3-(2,2-dimethylpropyl)-4,7,7-trimethyl-4-phenyl-2,6,8,9-tetrahydropyrazolo[3,4-b]quinolin-5-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: 200 mg/mL (529.77 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.24 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 (13.24 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6489 mL | 13.2443 mL | 26.4887 mL | |
| 5 mM | 0.5298 mL | 2.6489 mL | 5.2977 mL | |
| 10 mM | 0.2649 mL | 1.3244 mL | 2.6489 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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