Succinobucol (AGI-1067)

Cell experiment:

The cytotoxicity of Succinobucol is determined in the metastatic 4T1 breast cancer cells. Cells are added to 96-well plates at 6×103 cells/well and cultured overnight. Then, Succinobucol, SCB and the PCD polymer (equivalent concentration to SCB) are respectively added to each well with SCB concentrations ranging from 4 ng/mL to 40 μg/mL. Cells without any treatment are performed as negative control. Thereafter, cells are incubated for further 48 h, and the cell viability is measured by MTT assay method.

Animal experiment:

Mice are injected with 2×105 4T1-luc cells per mouse to generate the lung metastatic breast cancer model. After the inoculation, mice are divided into three groups (n=4), and respectively treated with saline, SCB solution and Succinobucol (40 mg/kg) by tail injection every three days. At day 12, the formation of lung metastasis is determined by in vivo bioluminescence measurements. Then, mice are autopsied and the lung tissues are removed. In each lung tissue, the visually detected metastatic nodules are counted. The inhibition of lung metastasis is calculated as the average metastatic nodules in Succinobucol or SCB group compared to that in saline group. Moreover, the histological examination is performed by H&E staining to detect the metastatic foci in the lungs.

References:

[1]. Houston SA, et al. An investigation of the antiplatelet effects of succinobucol (AGI-1067). Platelets. 2017 May;28(3):295-300.
[2]. Colle D, 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):1280-95.
[3]. Dan Z, et al. A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer. Theranostics. 2016 Jan 25;6(3):435-45.