SC79

SC79 is a selective and cell-permeable Akt activator which activates Akt phosphorylation and inhibits Akt membrane translocation.

Signaling Pathways >> PI3K/Akt/mTOR >> Akt

Research Areas >> Cancer

Akt

SC79 reduces neuronal excitotoxicity and prevents stroke-induced neuronal death. SC79 suppresses PHAKTM-GFP plasma membrane translocation, and enhances phosphorylation of all three Akt isoforms in HEK293, HeLa, HL60, NB4, and HsSulton (B cells) cells[1]. SC79 restores proliferation of BRAT1 knockdown cells, and reduces the production of superoxide in mitochondria of MitoSox positive cells[2].

SC79 (0.04 mg/g, i.p.) inhibits the cytosolic activation of Akt, and recapitulates the primary cellular function of Akt signaling, resulting in augmented neuronal survival, in the permanent focal cerebral ischemia mouse model[1].

HsSultan or NB4 cells (2.5×105) are plated in a 24-well plate in 500 μL of phenol red-free RPMI medium supplemented with 10% FBS. After incubation for 24 hours, each compound (8 µg/mL) is added and cultured for overnight (16-20 h). Fifty μLs of MTT solution (5 mg/mL in PBS) are added to each well. Following 2 hrs incubation, the purple formazan crystals are dissolved by directly adding in 500 μL of isopropanol with 0.1mol/LHCl to each well. After clearing the cell debris by centrifugation, the absorbance is measured at a wavelength of 570 nm.

The permanent focal cerebral ischemia is induced by middle cerebral artery occlusion (MCAO) essentially. Briefly, mice (C57 Black/6) weighing 17-25 g are anesthetized with 4% isoflurane/66% N2O/30% O2 and maintained with 1.5% isoflurane. Permanent focal ischemia is achieved as follows: a 2-mm hole is drilled at a site superior and lateral to the left foramen ovale to expose the left middle cerebral artery. The proximal portion of the left middle cerebral artery (MCA) is permanently occluded over a 1-mm segment distal to the origin of the lenticulostriate branches through the use of a bipolar coagulator. SC79 is injected intraperitoneally (0.04 mg/g mouse body weight) 5 min before permanent MCAO. In another experiment, extra SC79 is injected (0.04 mg/g mouse body weight, once per hour for 6 hours).

[1]. Jo H, 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):10581-10586.

[2]. So EY, et al. BRAT1 deficiency causes increased glucose metabolism and mitochondrial malfunction. BMC Cancer. 2014 Jul 29;14:548

SB203580 | MK-2206 2HCl | Capivasertib (AZD5363) | Honokiol | AKT inhibitor VIII | GDC-0068 | GSK690693 | Uprosertib | 1,3-Dicaffeoylquinic acid | TIC10 | Triciribine | Perifosine (KRX-0401) | afuresertib | A-443654 | Scutellarin