TDZD-8

TDZD-8是一种糖原合酶激酶3β(GSK-3β)抑制剂,其IC50值为1.4 μM[1].

TDZD-8是有效的和非ATP竞争性的GSK-3β抑制剂.相对于其它蛋白激酶,包括蛋白激酶A\酪蛋白激酶II和细胞周期蛋白依赖性激酶1(Cdk-1/cyclin B),TDZD-8对GSK-3β具有选择性.然而,TDZD-8也可以抑制蛋白激酶C的PKCβI和PKCδ亚型,相应IC50值为1.4 μM和1.1 μM[1,2].

在细胞实验中,TDZD-8抑制GSK-3β以及PKC,从而降低PDT诱导的神经元坏死和神经胶质细胞凋亡.此外,在多种原代人白血病细胞中,TDZD-8可能由于抑制了PKC和FLT3,从而具有抗白血病活性[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.