ONO 2506 (Arundic Acid)

ONO 2506 (Arundic Acid) is an orally active astrocyte modulator. ONO 2506 regulates astrocyte activation by inhibiting S-100β synthesis and upregulates EAAT1 expression by activating the Akt, ERK, and NF-κB pathways to reduce excitatory neurotoxicity. ONO 2506 can be used in research related to stroke and Alzheimer's disease^[1-4].

In vitro, 1321N1 astrocyte cells were pretreated with ONO 2506 (50μM) for 24 hours, followed by stimulation with Aβ25-35 (200μM) for 24 hours. ONO 2506 significantly ameliorated the gliotoxic effects of Aβ, increased cell viability, and decreased both intracellular and extracellular S100B levels^[5]. Mouse Müller cells were treated with ONO 2506 (0-100μM) for 14 days, or H4 human glioblastoma cells were treated with ONO 2506 (0-100μM) for 9 days. ONO 2506 significantly increased glutamate uptake activity, GLAST/EAAT1 mRNA and protein expression, and activated the EAAT1 promoter in H4 cells^[6].

In vivo, ONO 2506 (2μg/μl; at a dose of 0.5% of body weight) was administered via intracerebroventricular injection in a rat model of intracerebral hemorrhage. ONO 2506 improved motor dysfunction, reduced S100B levels, astrogliosis, and microglial activation, thereby decreasing the release of pro-inflammatory cytokines IL-1β and TNF-α and ROS production^[7]. ONO 2506 (30mg/kg) was administered intraperitoneally on days 3, 4, 5, and 6 after the last injection of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 20mg/kg; at 2-hour intervals; four times total) in C57BL/6 mice treated with MPTP. ONO 2506 ameliorated MPTP-induced neuronal damage in the striatum and substantia nigra and reduced astrogliosis and microglial activation^[8].

References:
[1] Karki P, Hong P, Johnson J Jr, et al. Arundic Acid Increases Expression and Function of Astrocytic Glutamate Transporter EAAT1 Via the ERK, Akt, and NF-κB Pathways. Mol Neurobiol. 2018 Jun;55(6):5031-5046.
[2] Kato H, Kurosaki R, Oki C, et al. Arundic acid, an astrocyte-modulating agent, protects dopaminergic neurons against MPTP neurotoxicity in mice. Brain Res. 2004 Dec 24;1030(1):66-73.
[3] Fernandes RA, Ingle AB. Arundic acid a potential neuroprotective agent: biological development and syntheses. Curr Med Chem. 2013;20(18):2315-29.
[4] Asano T, Mori T, Shimoda T, et al. Arundic acid (ONO-2506) ameliorates delayed ischemic brain damage by preventing astrocytic overproduction of S100B. Curr Drug Targets CNS Neurol Disord. 2005 Apr;4(2):127-42.
[5] Keshavarz M, Farrokhi MR, Amiri A, et al. The contribution of S100B to the glioprotective effects of valproic and arundic acids. Iran J Basic Med Sci. 2019 May;22(5):557-562.
[6] Yanagisawa M, Aida T, Takeda T, et al. Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma. Cell Death Dis. 2015 Mar 19;6(3):e1693.
[7] Cordeiro JL, Neves JD, Nicola F, et al. Arundic Acid (ONO-2506) Attenuates Neuroinflammation and Prevents Motor Impairment in Rats with Intracerebral Hemorrhage. Cell Mol Neurobiol. 2022 Apr;42(3):739-751.
[8] Oki C, Watanabe Y, Yokoyama H, et al. Delayed treatment with arundic acid reduces the MPTP-induced neurotoxicity in mice. Cell Mol Neurobiol. 2008 May;28(3):417-30.