SC 79

SC 79 is a specific, blood-brain barrier-permeable Akt agonist^[1]. SC 79 specifically binds to the PH domain of Akt, activates cytosolic Akt, while inhibiting Akt translocation to the plasma membrane^[2]. SC 79 has shown research utility in the fields of neuroprotection, ischemia-reperfusion injury, and apoptosis, and has demonstrated protective effects in animal models of stroke and liver injury^[3,4].

In vitro, SC 79 (4μg/mL) pretreatment of HepG2 cells for 30min, followed by co-treatment with TNF-α (0-16ng/mL) for 24h, significantly increased cell viability and reduced TUNEL-positive apoptotic cells^[5]. SC 79 (1-10μg/mL) treatment of ARPE-19 cells for 1h dose-dependently induced Akt phosphorylation (p-Akt Ser473) activation^[6].

In vivo, SC 79 (10mg/kg) pretreatment of C57BL/6 mice via intraperitoneal injection for 0.5h, followed by administration of D-galactosamine (400mg/kg) and lipopolysaccharide (LPS, 60μg/kg) to induce acute liver injury, significantly reduced hepatic caspase-3/7 activities in mice^[5]. SC 79 (10mg/kg) pretreatment of C57BL/6 mice via intraperitoneal injection for 0.5h, followed by administration of a lethal dose of anti-Fas Jo2 to induce acute liver failure, increased the 12h survival rate of mice from 0% to 35%, with no additional mortality observed through the end of the 2-month observation period^[7].

References:

[1] Zhu J, Wu Y, Wu D, et al. SC 79, a novel Akt activator, protects dopaminergic neuronal cells from MPP+ and rotenone[J]. Molecular and cellular biochemistry, 2019, 461(1): 81-89.

[2] Jo H, Mondal S, Tan D, et al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death[J]. Proceedings of the National Academy of Sciences, 2012, 109(26): 10581-10586.

[3] Luan Q, Pan L, He D, et al. SC 79, the AKT activator protects cerebral ischemia in a rat model of ischemia/reperfusion injury[J]. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 2018, 24: 5391.

[4] Xu Y, Gao Y W, Yang Y. SC 79 protects dopaminergic neurons from oxidative stress[J]. Oncotarget, 2017, 9(16): 12639.

[5] Jing Z T, Liu W, Xue C R, et al. AKT activator SC 79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2019, 316(3): G387-G396.

[6] Gong Y, Huang W, Li K, et al. SC 79 protects retinal pigment epithelium cells from UV radiation via activating Akt-Nrf2 signaling[J]. Oncotarget, 2016, 7(37): 60123.

[7] Liu W, Jing Z T, Wu S X, et al. A novel AKT activator, SC 79, prevents acute hepatic failure induced by Fas-mediated apoptosis of hepatocytes[J]. The American journal of pathology, 2018, 188(5): 1171-1182.