mediates the kinase activity, Tyrosine located at the C-terminal it essential for full GSK3 activity. Benefits of GSK-3β inhibitors In diabetes, GSK-3β inhibitors increase insulin sensitivity, glycogen synthesis, and glucose metabolism in skeletal muscles, and reduce obesity by affecting the adipogenesis process. GSK-3β is also over expressed in several types of cancers, like colorectal, ovarian, and prostate cancer. GSK-3β inhibitors also aid in the treatment of Alzheimer's disease, stroke, and mood disorders, including bipolar disorder. Specific agents Inhibitors of GSK-3 include: Metal cations Beryllium Copper Lithium (IC50=2mM) Mercury Tungsten (Indirect) Zinc (IC50=15μM) ATP-competitive Marine organism-derived 6-BIO (IC50=1.5μM) Dibromocantharelline (IC50=3μM) Hymenialdesine (IC50=10nM) Indirubin (IC50=5-50nM) Meridianin Aminopyrimidines CHIR99021 (IC50=6.9nM-10nM) CHIR98014 (IC50=0.58-0.65nM) CT98014 CT98023 CT99021 TWS119 (IC50=30nM) Arylindolemaleimide SB-216763 (IC50=34nM) SB-41528 (IC50=31-78nM) Thiazoles AR-A014418 (IC50=104nM) AZD-1080 (IC50=6.9nM-31nM) Paullones IC50=4-80nM: Alsterpaullone Cazpaullone Kenpaullone Aloisines IC50=0.5-1.5μM: Non-ATP competitive Marine organism-derived Manzamine A (IC50=1.5μM) Palinurine (IC50=4.5μM) Tricantine (IC50=7.5μM) Thiazolidinediones TDZD-8 (IC50=2μM) NP00111 (IC50=2μM) NP031115 (IC50=4μM) Tideglusib (IC50=60nM) Halomethylketones HMK-32 (IC50=1.5μM) Peptides L803-mts (IC50=20μM) L807-mts (IC50=1μM) Unknown Mechanism (small-molecule inhibitors) COB-187 (IC50=11nM-22nM) COB-152 (IC50=77nM-132nM) Lithium Lithium which is used in the treatment of bipolar disorder was the first natural GSK-3 inhibitor discovered. It inhibits GSK-3 directly by competition with magnesium ions and indirectly by phosphorylation and auto-regulation of serine. Lithium has been found to have insulin-like effects on glucose metabolism, including stimulation of glycogen synthesis in fat cells, skin, and muscles, increasing glucose uptake, and activation of GS activity. In addition to inhibition of GSK-3, it also inhibits other enzymes involved in the regulation of glucose metabolisms, such as myo-inositol-1-monophosphatase and 1,6 bisphosphatase. Also, it has shown therapeutic benefit in Alzheimer's and other neurodegenerative diseases such as epileptic neurodegeneration. Naproxen and Cromolyn Naproxen is a non-steroidal anti-inflammatory drug while cromolyn is an anti-allergic agent which acts as a mast cell stabilizer. Both drugs have demonstrated the anticancer effect in addition to hypoglycemic effect due to inhibition of glycogen synthase kinase-3β (GSK-3β). To validate the anti-GSK-3β hypothesis of naproxen and cromolyn, docking of the two structures against GSK-3β binding pocket and comparing their fitting with known GSK-3β inhibitor ARA014418 was performed, in addition to measuring the serum glucose, serum insulin, serum C-peptide, weight variation and hepatic glycogen levels for normal and diabetic fasting animal's models to assess their in vitro hypoglycemic effects. Naproxen and cromolyn were successfully docked into the binding site of GSK-3β (both were fitted into its binding pocket). They exhibited electrostatic, hydrophobic, and hydrogen-bonding interactions