SC 79

SC 79 is an activator of osmotic Akt phosphorylation in the brain and an inhibitor of AKT-PH domain translocation^[1].

SC 79 enhances phosphorylation of all three Akt isotypes and enhances Akt activation in a variety of cell types^[1]. Treatment of BRAT1 knockdown cells with Akt activator SC 79 can improve their proliferation and reduces mitochondrial ROS concentration[4]. In both SH-SY5Y cells and primary murine dopaminergic neurons, pre-treatment with SC 79 largely inhibited hydrogen peroxide (H2O2)-induced cell viability reduction, apoptosis and necrosis. SC 79 activated Akt in the neuronal cells, which was required for its neuroprotection against H2O2[5]. In primary murine osteoblasts and osteoblastic MC3T3-E1 cells, pretreatment with SC 79 significantly attenuated Dex-induced cell death. Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening, cytochrome C release and apoptosis activation were dramatically alleviated with SC 79 pretreatment in above cells[6]. The protective role of SC 79 against H/R of hepatocytes or hepatic I/R injury is related to activation of phosphorylation of Akt, resulting in the decrease of pro-apoptotic protein of Bim, Bax, and Bad, and increase of the anti-apoptotic protein Bcl-2 and Bcl-xL induced by cell H/R and hepatic I/R injury[7].

SC 79 enhances Akt activity during neuronal cell death in an in vivo mouse model of ischemia, SC 79 attenuates stroke-induced neuron death^[1]. SC 79 protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2^[2]. Akt activator SC 79 protects hepatocytes from TNF-α-induced apoptosis and protects mice from d-galactosamine (d-Gal)/lipopolysaccharide (LPS)-induced TNF-α-mediated liver injury and damage. SC 79 not only enhances the nuclear factor-κB (NF-κB) prosurvival signaling in response to TNF-α stimulation, but also increases the expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein L and S (FLIPL/S), which consequently inhibits the activation of procaspase-8^[2].

References:
[1]: Jo H, Mondal S, et,al. Small molecule-induced cytosolic activation of protein kinase Akt rescues ischemia-elicited neuronal death. Proc Natl Acad Sci U S A. 2012 Jun 26;109(26):10581-6. doi: 10.1073/pnas.1202810109. Epub 2012 Jun 11. PMID: 22689977; PMCID: PMC3387065.
[2]: Liu W, Jing ZT, et,al. A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes. Am J Pathol. 2018 May;188(5):1171-1182. doi: 10.1016/j.ajpath.2018.01.013. PMID: 29673487.
[3]: Jing ZT, Liu W, et,al. AKT activator SC79 protects hepatocytes from TNF-α-mediated apoptosis and alleviates d-Gal/LPS-induced liver injury. Am J Physiol Gastrointest Liver Physiol. 2019 Mar 1;316(3):G387-G396. doi: 10.1152/ajpgi.00350.2018. Epub 2019 Jan 10. PMID: 30629471.
[4]: So EY, Ouchi T. BRAT1 deficiency causes increased glucose metabolism and mitochondrial malfunction. BMC Cancer. 2014 Jul 29;14:548. doi: 10.1186/1471-2407-14-548. PMID: 25070371; PMCID: PMC4129107.
[5]: Xu Y, Gao YW, et,al. SC79 protects dopaminergic neurons from oxidative stress. Oncotarget. 2017 Dec 20;9(16):12639-12648. doi: 10.18632/oncotarget.23538. PMID: 29560097; PMCID: PMC5849161.
[6]: Li ST, Chen NN, et,al. SC79 rescues osteoblasts from dexamethasone though activating Akt-Nrf2 signaling. Biochem Biophys Res Commun. 2016 Oct 7;479(1):54-60. doi: 10.1016/j.bbrc.2016.09.027. Epub 2016 Sep 7. PMID: 27614310.
[7]: Zhou H, Yu Y,et,al. Protective Effects the Akt Activator SC79 in Hepatic Ischemia-Reperfusion Injury. Med Sci Monit. 2018 Jun 24;24:4346-4354. doi: 10.12659/MSM.911178. PMID: 29936516; PMCID: PMC6049012.