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GSK-3 Inhibitor IX (BIO)

现货
Catalog No.
B1538
GSK-3α和GSK-3β抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,080.00
现货
10mg
¥ 1,030.00
现货
50mg
¥ 3,990.00
现货

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Background

GSK-3 inhibitor IX (BIO) is a potent, selective, cell-permeable, ATP-competitive and reversible inhibitor of GSK-3α (glycogen synthase kinase-3α) and GSK-3β (lycogen synthase kinase-3β) (IC50 = 5nM for GSK-3β). [1]

GSK3 (glycogen synthase kinase-3) is a serine/threonine protein kinase which contributes to cell survival, diabetes, insulin resistance and Alzheimer's diseases. It is contributed to β-catenin/Wnt signaling pathway.

BIO facilitated the proliferation in mammalian cardiomyocytes by increasing the proliferation potential of cardiomyocytes. It induced S phase entry and beta-catenin activity in neonatal cardiomyocyte. [3] BIO also activated Wnt signaling and involved in maintaining pluripotency in human and mouse ESCs (embryonic stem cells). [2] In Cos-1 cells treated with 5 μm BIO for 24 hours, phosphorylation of β-catenin was inhibited on GSK-3 specific sites. In cell line deficient for AhR or ARNT, 10 μm BIO treatment for 24 hours showed its effect is through a direct and AhR- independent pathway.[1]

In vivo study showed BIO activated maternal Wnt signaling pathway in Xenopus embryos. It caused a hyper dorso-anteriorization at the expense of trunk and tail in a dose-response manner. It also activated the dorsal genes (siamois and chordin) ectopically. [1]

References:
[1] Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R, Crovace C, Tarricone C, Musacchio A, Roe SM, Pearl L, Greengard P.  GSK-3-selective inhibitors derived from Tyrian purple indirubins.  Chem Biol. 2003 Dec;10(12):1255-66.
[2] Sato N, Meijer L, Skaltsounis L, Greengard P, Brivanlou AH.  Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor.  Nat Med. 2004 Jan;10(1):55-63. 
[3] Tseng AS, Engel FB, Keating MT.  The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes.  Chem Biol. 2006 Sep;13(9):957-63.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt356.17
Cas No.667463-62-9
FormulaC16H10BrN3O2
SynonymsGSK-3 Inhibitor IX
Solubility≥35.6 mg/mL in DMSO, ≥14.4 mg/mL in EtOH with gentle warming, <1.78 mg/mL in H2O
Chemical Name6-bromo-3-[3-(hydroxyamino)indol-2-ylidene]-1H-indol-2-one
SDFDownload SDF
Canonical SMILESC1=CC2=C(C(=C3C4=C(C=C(C=C4)Br)NC3=O)N=C2C=C1)NO
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

激酶实验

在30℃,ATP终浓度为15 μM、缓冲液A或C(除非另有说明)中测定激酶活性。减去空白值,活性计算为在孵育10分钟内掺入的磷酸pmol。 活性通常以最大活性的百分比表示,即在没有抑制剂的情况下,用适当的二甲基亚砜稀释液做对照。在少数情况下,在SDS-PAGE后通过放射自显影评估底物的磷酸化水平。通过在固定化轴蛋白[S1]上的亲和层析从猪脑中纯化GSK-3α/β。 反应条件为在1mg BSA / ml 10mM DTT中1/100稀释后,用特异性GSK-3底物,5μl、40μM GS-1肽(YRRAAVPPSPSLSRHSSPHQSpEDEEE,由Peptide Synthesis Unit,Institute of Biomolecular Science,University of Southampton,UK公司合成)在缓冲液A、15μM[γ-32P] ATP(3,000Ci / mmol; 1mCi / ml)存在下,在30μl的终体积中,在30℃温育30分钟后,将25μl等分的上清液点样到2.5×3cm的Whatman P81磷酸纤维素纸上,并且20秒后,将滤器在10ml磷酸/升水的溶液中洗涤五次(每次至少5分钟),在1ml ACS(Amersham)闪烁液的存在下计数湿滤器。

细胞实验:

细胞系

Cos-1细胞、SH-SY5Y细胞、成年大鼠哺乳动物心肌细胞

溶解方法

该化合物在DMSO中的溶解度> 10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应时间

5,10 μM处理24小时;或1 μM处理12小时;5 μM处理48小时

应用

选择性GSK-3抑制剂BIO抑制Cos-1细胞中β-连环蛋白对GSK-3特异性位点的磷酸化;此外,BIO显著降低GSK-3两种亚型的酪氨酸磷酸化水平 [1]。 BIO还增加了哺乳动物心肌细胞的增殖潜力 [2]。

动物实验:

动物模型

非洲爪蟾胚胎模型

剂量

5、15和50 μM

应用

BIO是体内GSK-3活性的有效和特异性抑制剂,BIO激活非洲爪蟾胚胎中的母体Wnt信号通路 [1]。

注意事项

请于室内测试所有化合物的溶解度。实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

References:

1Meijer, L., Skaltsounis, A. L., Magiatis, P., Polychronopoulos, P., Knockaert, M., Leost, M., Ryan, X. P., Vonica, C. A., Brivanlou, A., Dajani, R., Crovace, C., Tarricone, C., Musacchio, A., Roe, S. M., Pearl, L. and Greengard, P. (2003) GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol. 10, 1255-12662

2Tseng, A. S., Engel, F. B. and Keating, M. T. (2006) The GSK-3 inhibitor BIO promotes proliferation in mammalian cardiomyocytes. Chem Biol. 13, 957-963

质量控制

化学结构

GSK-3 Inhibitor IX (BIO)