Succinobucol (AGI-1067) is a vasoprotective agent and phenolic antioxidant. Succinobucol exerts anti-inflammatory effects by selectively inhibiting the expression of redox-sensitive genes in endothelial cells and monocytes through the suppression of ASK1 and the subsequent activation of downstream p38 and JNK MAP kinases. Succinobucol can be used in research related to atherosclerosis, coronary heart disease, type 2 diabetes, and restenosis after percutaneous coronary intervention[1-4].
In vitro, SH-SY5Y cells were pretreated with succinobucol (3μM) for 6 days, followed by stimulation with 3-nitropropionic acid (3-NP; 1mM) for 6 or 24 hours. Succinobucol significantly prevented 3-NP-induced loss of cellular viability, increased generation of reactive oxygen species, and decrease of mitochondrial membrane potential (ΔΨm), and increased glutathione levels and glutamate cysteine ligase activity[5]. Metastatic 4T1 breast cancer cells were treated with Succinobucol (400ng/mL) for 24 hours. Succinobucol significantly inhibited cell migration and invasion, reduced the expression of vascular cell adhesion molecule-1 (VCAM-1), and decreased the binding of RAW 264.7 monocytes to 4T1 cancer cells[6].
In vivo, Swiss mice received daily intraperitoneal injections of Succinobucol (10mg/kg/day) for 15 days following a single intracerebroventricular infusion of 6-OHDA (40μg/site). Succinobucol partially protected against 6-OHDA-induced forelimb inability[7]. C57BL/6 mice received daily oral gavage of Succinobucol (10mg/kg/day) for 45 days following intranasal MPTP infusion (1mg/nostril). Succinobucol significantly alleviated MPTP-induced behavioral impairments and prevented the reduction of tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoreactivity in the substantia nigra and striatum[8].
References:
[1] Auten RL, Richardson RM, White JR, et al. Nonpeptide CXCR2 antagonist prevents neutrophil accumulation in hyperoxia-exposed newborn rats. J Pharmacol Exp Ther. 2001 Oct;299(1):90-5.
[2] Muldrew KM, Franks AM. Succinobucol: review of the metabolic, antiplatelet and cardiovascular effects. Expert Opin Investig Drugs. 2009 Apr;18(4):531-9.
[3] Dan Z, Cao H, He X, et al. A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer. Theranostics. 2016 Jan 25;6(3):435-45.
[4] Tardif JC. Clinical results with AGI-1067: a novel antioxidant vascular protectant. Am J Cardiol. 2003 Feb 6;91(3A):41A-49A.
[5] Colle D, Santos DB, Hartwig JM, et al. Succinobucol, a Lipid-Lowering Drug, Protects Against 3-Nitropropionic Acid-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Cells via Upregulation of Glutathione Levels and Glutamate Cysteine Ligase Activity. Mol Neurobiol. 2016 Mar;53(2):1280-1295.
[6] He X, Yu H, Bao X, et al. pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer. Adv Healthc Mater. 2016 Feb 18;5(4):439-48.
[7] Ribeiro RP, Santos DB, Colle D, et al. Decreased forelimb ability in mice intracerebroventricularly injected with low dose 6-hydroxidopamine: A model on the dissociation of bradykinesia from hypokinesia. Behav Brain Res. 2016 May 15;305:30-6.
[8] Santos DB, Colle D, Moreira EL, et al. Succinobucol, a Non-Statin Hypocholesterolemic Drug, Prevents Premotor Symptoms and Nigrostriatal Neurodegeneration in an Experimental Model of Parkinson's Disease. Mol Neurobiol. 2017 Mar;54(2):1513-1530.