| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
GSK-3β 15 nM (IC50) GSK-3α 215 nM (IC50)
GSK3beta (glycogen synthase kinase 3 beta). BRD3731 is a selective GSK3beta inhibitor with IC50 values of 15 nM for GSK3beta and 215 nM for GSK3alpha, demonstrating approximately 14-fold selectivity for the beta isoform. |
|---|---|
| ln Vitro |
BRD3731 is a GSK3β-selective inhibitor retrieved from patent US20160375006A1, compound example 272[1]. BRD3731 (1-10 μM; 24 h) suppresses the phosphorylation of CRMP2 in SH-SY5Y cells [1]. BRD3731 (20 μM; 24 hours) lowers β-catenin S33/37/T41 phosphorylation and increases β-catenin S675 phosphorylation in HL-60 cells [2]. BRD3731 (10 -20 μM; 7-10 days) inhibits colony formation in TF-1 and enhances colony formation in the MV4-11 cell line [2].
BRD3731 (1-10 uM; 24 h) inhibits the phosphorylation of CRMP2 in SH-SY5Y cells. In HL-60 cells, BRD3731 (20 uM; 24 h) decreases beta-catenin phosphorylation at S33/37/T41 and induces beta-catenin S675 phosphorylation. In colony formation assays, BRD3731 (10-20 uM; 7-10 days) impairs colony formation in TF-1 cells but increases colony-forming ability in the MV4-11 cell line. |
| ln Vivo |
No specific in vivo efficacy data are reported for BRD3731 in the literature. Based on its selectivity and oral bioavailability, it is hypothesized to have therapeutic potential in animal models of PTSD, psychiatric disorders, diabetes, and neurodegeneration; however, such in vivo studies have not been published for this specific compound.
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| Enzyme Assay |
Cell-free GSK3beta activity assays are performed using recombinant human GSK3beta or GSK3alpha enzymes. The enzyme is incubated with a biotinylated peptide substrate (derived from glycogen synthase, e.g., YRRAAVPPSPSLSRHSSPHQS(P)EDEEE) and ATP in the presence of increasing concentrations of BRD3731 (0.01-10,000 nM) in assay buffer (50 mM HEPES, pH 7.4, 10 mM MgCl2, 0.01% Brij-35). The reaction is quenched, and phosphorylated product is detected by TR-FRET using a phospho-substrate antibody and terbium-labeled detection reagent. IC50 is calculated by nonlinear regression.
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| Cell Assay |
SH-SY5Y neuroblastoma cells are seeded and treated with BRD3731 (1-10 uM) for 24 hours. Cells are lysed, and protein lysates are subjected to Western blot analysis to assess the phosphorylation status of CRMP2 (collapsin response mediator protein 2) and other GSK3beta downstream targets (e.g., beta-catenin). Band densities are quantified and normalized to total protein or housekeeping controls (GAPDH).
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| Animal Protocol |
No published in vivo animal protocols are available for BRD3731. For standard GSK3 inhibitor studies, BRD3731 would likely be administered to rodents via oral gavage at doses ranging from 10-100 mg/kg. Blood and brain tissue would be collected at various time points (0-24 h) for LC-MS/MS analysis. Efficacy could be evaluated in behavioral models relevant to PTSD or cognitive function, but such studies have not been reported.
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| ADME/Pharmacokinetics |
Pharmacokinetic data are not reported for BRD3731. The molecular weight is 377.52 (C24H31N3O). Based on supplier information, BRD3731 is described as orally bioavailable, suggesting adequate absorption and systemic exposure after oral administration. DMSO solubility: 50 mg/mL (132.44 mM). Storage: -20degC, dry, and protected from light. Formulation for in vivo studies has not been described.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for BRD3731. As a selective GSK3beta inhibitor, potential safety concerns include effects on glucose metabolism and glycogen synthesis, as GSK3 is a key regulator of these pathways. Standard safety assessments would include hERG channel inhibition (cardiotoxicity), CYP inhibition (DDI potential), and genotoxicity (Ames test). No clinical trials have been conducted.
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| References | |
| Additional Infomation |
Other information: BRD3731 is a research compound, not FDA-approved. It is derived from patent US20160375006A1 (compound example 272). The compound is available for research use only, with purity ≥98% (CAS 2056262-07-6). Synonyms: (S)-BRD3731 (since it contains an S-chiral center based on the chemical structure). For research purposes only.
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| Molecular Formula |
C24H31N3O
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|---|---|
| Molecular Weight |
377.5224
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| Exact Mass |
377.246
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| CAS # |
2056262-07-6
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| Related CAS # |
(R)-BRD3731;2056262-08-7
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| PubChem CID |
135567205
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
668
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C2=C1[C@@](C([H])([H])[H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1=C(C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])N([H])N=C1N2[H]
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| InChi Key |
YZRXTIGAQRIAEX-XMMPIXPASA-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-/m1/s1
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| Chemical Name |
(4S)-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: 50 mg/mL (132.44 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) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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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