ARN25657
ARN25657 is a dual-acting D3R/GSK-3β modulator. ARN25657 has both partial D3R agonist activity (EC50 = 15.2 nM, Ki =1.5 nM) and potent GSK-3β inhibitor activity (IC50 = 19.3 nM). ARN25657 exhibits excellent GSK-3β selectivity over FYN, PKA, and CDK5/p35. ARN25657 inhibits P-glycoprotein (P-gP)-mediated acetoxymethyl calcein efflux and improves in vitro ADME properties while maintaining a balanced dual-target profile. ARN25657 is useful for studying bipolar disorder and related neuropsychiatric disorders.
For research use only. We do not sell to patients.
- Formula: C26H28N6O2
- Molecular Weight:456.54
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All Dopamine Receptor Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
D3 Receptor 15.2 nM (EC50) |
D3 Receptor 1.5 nM (Ki) |
GSK-3β 19.3 nM (IC50) |
In Vitro
ARN25657 (Compound 16) (1 μM, 10 μM) inhibits P-gp-mediated efflux of acetoxymethyl calcein efflux in MDR1-MDCKII cells, logD = 1.84, inhibition percentage 10.9 % at 10 μM[1].
ARN25657 (1 μM, 5 μM, 3 h) inhibits GSK-3β activity in neuronal SH-SY5Y cells[1].
ARN25657 (10 nM, 100 nM) exhibits high affinity for D3R (68 % inhibition of binding of (+)-butaclamol; Ki = 1.5 nM) at 100 nM in CHO cells and D2R at 10 nM (80 % inhibition of [3H]7-OH-DPAT binding; Ki = 1 nM) in HEK293 cells[1].
ARN25657 (0.1 μM, 10 μM) exhibits excellent GSK-3β selectivity over FYN, PKA and CDK5/p35 with selectivity ratio (compared to GSK-3β at 0.1 μM) of 0 h, 0.1 h, 0 h respectively in a KinaseProfiler assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:Neuronal SH-SY5Y cells
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Concentration:1 μM, 5 μM
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Incubation Time:3 h
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Result:Increased the inactive phospho-GSK-3α/β (Ser21/9) form.
Parmacokinetics
| Species | Dose | Route | Tmax | Cmax | AUC | F | Vd | T1/2 | CL |
|---|---|---|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | p.o. | 15 min | 678 ng/mL | 24957 min·ng/mL | 15 % | 95.6 L/kg | 180 min | 368 mL/min/kg |
| Mice | 3 mg/kg | i.v. | 5 min | 1429 ng/mL | 49493 min·ng/mL | 15 % | 3.3 L/kg | 38 min | 60 mL/min/kg |
Chemical Information
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Molecular Weight 456.54
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Formula C26H28N6O2
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SMILES
O=C(N(C1=CC(C2=CC=CN=C2)=CC=C1N3)C3=O)NCCCN4CCN(C5=CC=CC=C5)CC4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Protocol for Pharmacokinetic Study
Pharmacokinetic studies quantify how an organism handles a drug over time through absorption, distribution, metabolism, and excretion, and the core experimental readout is the concentration-time profile of parent drug and, when relevant, metabolites in biological matrices such as plasma, whole blood, urine, bile, or tissue. Pharmacokinetic analysis links dose, route, exposure, clearance, half-life, distribution, bioavailability, and systemic exposure to drug efficacy and toxicity hypotheses rather than measuring a signaling pathway directly. The literature links pharmacokinetics to drug-development phenotypes by showing that drug metabolism and pharmacokinetics influence compound progression, exposure-response interpretation, safety margins, dosing strategy, and failure risk during discovery and development. DMPK science contributes to compound optimization by integrating physicochemical properties, in vitro metabolism, transporter behavior, in vivo exposure, and pharmacodynamic contex
Purity & Documentation
References
[1]. Di Martino RMC, et al. Rational optimization of D3R/GSK-3β dual target-directed ligands as potential treatment for bipolar disorder: Design, synthesis, X-ray crystallography, molecular dynamics simulations, in vitro ADME, and in vivo pharmacokinetic studies. Eur J Med Chem. 2025 Jun 25;297:117899. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)