GSK-3 Inhibitor IX (BIO) is a potent, selective and reversible inhibitor of glycogen synthase kinase-3 (GSK-3) with an IC50 value of 5nM for GSK-3α/β[1]. GSK-3 is a serine/threonine protein kinase and one of the protein kinases with the most substrates in cells. GSK-3 is associated with a variety of diseases, such as cancer, Alzheimer's disease, bipolar disorder (BPD), Parkinson's disease, aging, inflammation and metabolic diseases[2]. GSK-3 Inhibitor IX is the first pharmacological agent that can maintain the self-renewal of human and mouse embryonic stem cells (ESCs)[3]. GSK-3 Inhibitor IX can promote the proliferation of mammalian cardiomyocytes[4].
In vitro, GSK-3 Inhibitor IX (0-20µM) treated human melanoma cells (A2058 cells) for 24h reduced cell viability in a dose-dependent manner with an IC50 value of approximately 5µM, reduced the expression of the anti-apoptotic protein Mcl-1 in the cells, and inhibited the phosphorylation of Janus-activated kinase (JAK) family members JAK1, JAK2, and TYK2[5].
In vivo, GSK-3 Inhibitor IX (50mg/kg/day) was orally treated for 2 weeks in mice bearing melanoma cell xenografts, significantly inhibiting tumor growth in the mice[5].
References:
[1] Meijer L, Skaltsounis A L, Magiatis P, et al. GSK-3-selective inhibitors derived from Tyrian purple indirubins[J]. Chemistry & biology, 2003, 10(12): 1255-1266.
[2] Wang L, Li J, Di L. Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases[J]. Medicinal research reviews, 2022, 42(2): 946-982.
[3] Zhu H, Liu C, Sun J, et al. Effect of GSK-3 inhibitor on the proliferation of multipotent male germ line stem cells (mGSCs) derived from goat testis[J]. Theriogenology, 2012, 77(9): 1939-1950.
[4] Tseng A S, Engel F B, Keating M T. The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes[J]. Chemistry & biology, 2006, 13(9): 957-963.
[5] Liu L, Nam S, Tian Y, et al. 6-Bromoindirubin-3′-oxime inhibits JAK/STAT3 signaling and induces apoptosis of human melanoma cells[J]. Cancer research, 2011, 71(11): 3972-3979.
GSK-3 Inhibitor IX (BIO)是一种强效、选择性和可逆的糖原合成酶激酶-3（GSK-3）抑制剂，对GSK-3α/β的IC50值为5nM[1]。GSK-3是一种丝氨酸/苏氨酸蛋白激酶，是细胞中底物最多的蛋白激酶之一，GSK-3与多种疾病有关，例如癌症、阿尔茨海默氏病、双相情感障碍（BPD）、帕金森氏病、衰老、炎症和代谢疾病等[2]。GSK-3 Inhibitor IX是第一种能够维持人和小鼠胚胎干细胞（ESC）自我更新的药理学试剂[3]。GSK-3 Inhibitor IX能够促进哺乳动物心肌细胞增殖[4]。
在体外，GSK-3 Inhibitor IX（0-20µM）处理人黑色素瘤细胞（A2058细胞）24h，以剂量依赖性方式降低了细胞活力，IC50值约为5µM，降低了细胞内抗凋亡蛋白Mcl-1的表达，抑制了Janus激活激酶（JAK）家族JAK1、JAK2和TYK2的磷酸化[5]。
在体内，GSK-3 Inhibitor IX（50mg/kg/day）通过口服治疗黑色素瘤细胞异种移植小鼠2周，显著抑制了小鼠体内肿瘤的生长[5]。