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-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^[1].

ARN25657 (Compound 16) (1 μM，10 μM) 可抑制 MDR1-MDCKII 细胞中 P-gp 介导的乙酰氧甲基钙黄绿素外排，logD = 1.84，10 μM 时抑制率为 10.9%^[1]。

ARN25657 (1 μM，5 μM，3 小时) 可抑制神经元 SH-SY5Y 细胞中的 GSK-3β 活性^[1]。

ARN25657 (10 nM, 100 nM) 在 CHO 细胞中对 D3R 表现出高亲和力 ((+)-butaclamol 结合抑制率为 68%；K_i = 1.5 nM)，在 HEK293 细胞中对 D2R 表现出高亲和力 ([³H]7-OH-DPAT 结合抑制率为 80%；K_i = 1 nM)^[1]。

ARN25657 (0.1 μM, 10 μM) 对 FYN、PKA 和 CDK5/p35 表现出优异的 GSK-3β 选择性，在 KinaseProfiler 测定中，与 0.1 μM 的 GSK-3β 相比，选择性比分别为 0 h、0.1 h 和 0 h^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

456.54

C₂₆H₂₈N₆O₂

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]