We found that SB216763 increased the antioxidant defense in oxygen-deprived nerves, and specially evoked a powerful induction of SOD2. PGC 1a can Erlotinib solubility potently encourage endogenous antioxidant genes. This entirely prevented the generation of mitochondrial superoxide. Constant increased superoxide development does occur in the peri infarct area after the on-set of pMCAO and plays an integral role in the pathophysiological cascade resulting in ischemic neuronal injury. Noticeably, SB216763 behaved as a logical neuroprotectant in rats subjected to focal cerebral ischemia. We found a biphasic dose response in SB216763 mediated neuroprotection, with maximum influence at intermediate doses, without proof shift toward toxicity at higher doses. Such Ushaped dose response curves have been previously observed for other GSK Protein biosynthesis and 3b modulators aren’t unusual within the location of stroke studies in animals, as recently discussed with implications for drug development. SB216763 has been previously noted to cross the blood brain barrier after intraperitoneal injection. Although long-term pharmacological inhibition of GSK 3 lowers elevated blood glucose in diabetic rodents, acute intravenous application of SB216763 did not change blood glucose levels nor mean arterial pressure around 2 h after heart ischemia reperfusion in diabetic or non diabetic rodents, indicating the better outcome of cerebral ischemia noticed in our study isn’t influenced by confounding systemic effects. Glycogen synthase kinase 3b is increasingly being accepted as an attractive target for drug discovery, with prominence in treating neurological disorders. The multiple roles of the molecule in various signalling pathways enhance the dilemma of selectivity. Strongest GSK 3 inhibitors also prevent Cdks because of the large homology of the ATPbinding sites. This is true also for BIO and SB216763 at higher doses. But, SB216763 and BIO are several times more selective for Cabozantinib XL184 GSK 3 than for Cdks. AR A014418 is known as being one of the most selective GSK 3b chemical compounds. Further, there is considerable evidence that double GSK 3/Cdk inhibitors may be desirable for ischemic stroke therapy. A significant requirement is that, to avoid previous fails in translational swing medicine, future approaches to neuroprotection in cerebral ischemia contemplate polytherapies or drugs exhibiting an extensive action function at diverse points of the pathologic ischemic cascade. Among likely choice drugs, GSK 3 inhibitors deserve special interest. Previous studies have demonstrated that GSK 3b inhibition exerts its favorable effects at the level, by modulating Bcl 2 family proteins and increasing the ROS patience for mitochondrial permeability transition pore opening.