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| Targets |
BRD0209 targets glycogen synthase kinase 3 alpha and beta (GSK3α/β), two highly similar paralogs that are key regulatory kinases in the canonical Wnt pathway. It acts as a reversible ATP-competitive inhibitor, binding to the ATP-binding domain of GSK3β and exploiting a unique Glu-to-Asp amino acid "switch" in the hinge region of GSK3 paralogues to achieve selectivity. The compound demonstrates IC50 values of 19 nM for GSK3α and 5 nM for GSK3β, with a Ki of 4.2 nM.
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| ln Vitro |
In vitro, BRD0209 shows concentration-dependent inhibition of Tau phosphorylation with cellular EC50s of 1.76 μM in SH-SY5Y cells as measured by ELISA. Treatment of SH-SY5Y cells with BRD0209 at 10 μM significantly inhibits GSK3 kinase activity within 30 minutes, as evidenced by decreased phospho-CRMP2 and phospho-β-catenin levels. Prolonged exposure (24 hours) causes a dramatic decrease in autophosphorylation at Tyr279 (pGSK3α) and Tyr216 (pGSK3β).
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| ln Vivo |
In vivo, BRD0209 has demonstrated efficacy in a dopaminergic signaling paradigm modeling mood-related disorders. The compound shows potential for the research of mood disorder diseases. As a highly selective GSK3 inhibitor with unparalleled kinome-wide selectivity, BRD0209 opens the way for exclusive analyses of GSK3 function in multiple signaling pathways involved in various prevalent disorders.
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| Enzyme Assay |
In vitro enzyme or receptor binding assays for BRD0209 involve measuring its inhibition of GSK3 kinase activity. The assay typically uses purified recombinant GSK3α or GSK3β enzymes and a peptide substrate in the presence of ATP. Kinase activity is monitored by measuring the phosphorylation of the substrate using radioactive (e.g., 33P-ATP) or luminescent methods. The compound is incubated with the enzyme and substrate at various concentrations to determine IC50 values, which are 19 nM for GSK3α and 5 nM for GSK3β. Ki values are determined using kinetic analysis, with BRD0209 showing a Ki of 4.2 nM.
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| Cell Assay |
In vitro cell-based assays for BRD0209 are performed using SH-SY5Y neuroblastoma cells. Cells are treated with BRD0209 at concentrations ranging from sub-micromolar to 10 μM. The inhibition of GSK3 activity is assessed by measuring the phosphorylation of downstream substrates such as CRMP2 and β-catenin via Western blotting. Tau phosphorylation is measured using ELISA with cellular EC50s of 1.76 μM. Autophosphorylation at Tyr279 (GSK3α) and Tyr216 (GSK3β) is assessed after 24-hour exposure.
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| Animal Protocol |
In vivo animal experiments for BRD0209 are conducted using rodent models of mood-related disorders. The compound is typically formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline at a concentration of 1 mg/mL (2.88 mM). Administration routes and dosing regimens vary depending on the experimental paradigm. Efficacy is assessed by measuring behavioral outcomes in dopaminergic signaling models and by analyzing biochemical markers of GSK3 inhibition in brain tissue.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of BRD0209 indicate it is soluble in DMSO and can be formulated for in vivo administration. The compound has a molecular weight of 347.45 and a molecular formula of C22H25N3O. It has a LogP of 4.2. The powder is stable when stored at -20°C for up to 3 years or at 4°C for up to 2 years. In solvent, it can be stored at -80°C for 1 year. The compound is typically administered via intraperitoneal or oral routes in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for BRD0209 are characteristic of a research compound. As a highly selective GSK3 inhibitor, its safety profile is an important consideration for its development as a therapeutic agent. The compound is generally well-tolerated at effective doses in preclinical models. However, as with all kinase inhibitors, potential off-target effects and long-term safety require thorough evaluation. The compound is for research use only and not for human or veterinary use.
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| References | |
| Additional Infomation |
Other information: BRD0209 is also known as BRD-0209 and BRD 0209. It was developed by researchers who also identified the related compound BRD1652. The compound features a novel pyrazolo-tetrahydroquinolinone scaffold with unparalleled kinome-wide selectivity for GSK3 kinases. The IUPAC name is (S)-3-Cyclopropyl-4,7,7-trimethyl-4-phenyl-2,4,6,7,8,9-hexahydro-pyrazolo[3,4-b]quinolin-5-one. Its CAS number is 1597439-87-6.
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| Molecular Formula |
C22H25N3O
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|---|---|
| Molecular Weight |
347.45340514183
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| Exact Mass |
347.199
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| CAS # |
1597439-87-6
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| PubChem CID |
135567204
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.2
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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 |
2
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| Heavy Atom Count |
26
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| Complexity |
644
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1CC(C)(C)CC2=C1[C@](C1C=CC=CC=1)(C)C1C(=NNC=1C1CC1)N2
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| InChi Key |
YKPIWOGXCSQLFH-JOCHJYFZSA-N
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| InChi Code |
InChI=1S/C22H25N3O/c1-21(2)11-15-17(16(26)12-21)22(3,14-7-5-4-6-8-14)18-19(13-9-10-13)24-25-20(18)23-15/h4-8,13H,9-12H2,1-3H3,(H2,23,24,25)/t22-/m1/s1
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| Chemical Name |
(S)-3-Cyclopropyl-4,7,7-trimethyl-4-phenyl-2,4,6,7,8,9-hexahydro-pyrazolo[3,4-b]quinolin-5-one
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| Synonyms |
BRD0209 BRD-0209 BRD 0209
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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 : ~62.5 mg/mL (~179.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.99 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 20.8 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: ≥ 2.08 mg/mL (5.99 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 20.8 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: ≥ 2.08 mg/mL (5.99 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 | 2.8781 mL | 14.3906 mL | 28.7811 mL | |
| 5 mM | 0.5756 mL | 2.8781 mL | 5.7562 mL | |
| 10 mM | 0.2878 mL | 1.4391 mL | 2.8781 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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