Background:

TDZD-8 is an inhibitor of glycogen synthase kinase-3β (GSK-3β) with IC50 value of 1.4μM [1].

TDZD-8 is a potent inhibitor of GSK-3β. It is found to act as a noncompetitive inhibitor of ATP binding. TDZD-8 is selective against GSK-3β over other protein kinases including PKA, casein kinase II and cyclin dependent kinase 1 (Cdk-1/cyclin B). However, it is also reported that TDZD-8 can inhibit the protein kinase C isoforms PKCβI and PKCδ with IC50 values of 1.4μM and 1.1μM, respectively [1, 2].

In cellular assay, TDZD-8 is found to decrease PDT-induced necrosis of neurons and decrease PDT-induced apoptosis of glial cells through inhibiting GSK-3β as well as PKC. Besides that, TDZD-8 also has anti-leukemia activity in many primary human leukemia cells. It is probably due to its inhibition of PKC and FLT3 [3].

参考文献:
[1] Komandirov M A, Knyazeva E A, Fedorenko Y P, et al. On the role of phosphatidylinositol 3-kinase, protein kinase b/Akt, and glycogen synthase kinase-3β in photodynamic injury of crayfish neurons and glial cells. Journal of Molecular Neuroscience, 2011, 45(2): 229-235.
[2] Martinez A, Alonso M, Castro A, et al. First non-ATP competitive glycogen synthase kinase 3 β (GSK-3β) inhibitors: thiadiazolidinones (TDZD) as potential drugs for the treatment of Alzheimer's disease. Journal of medicinal chemistry, 2002, 45(6): 1292-1299.
[3] Guzman M L, Li X, Corbett C A, et al. Rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8). Blood, 2007, 110(13): 4436-4444.