ARN25657 

ARN25657 is a dual-acting D3R/GSK-3β modulator. ARN25657 has both partial D3R agonist activity (EC₅₀ = 15.2 nM, K_i =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-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^[1].

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; K_i = 1.5 nM) at 100 nM in CHO cells and D2R at 10 nM (80 % inhibition of [³H]7-OH-DPAT binding; K_i = 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.

456.54

C₂₆H₂₈N₆O₂

O=C(N(C1=CC(C2=CC=CN=C2)=CC=C1N3)C3=O)NCCCN4CCN(C5=CC=CC=C5)CC4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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]