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SGI-1776 free base

现货
Catalog No.
A4192
ATP竞争性的Pim激酶抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,000.00
现货
5mg
¥ 900.00
现货
10mg
¥ 1,700.00
现货
50mg
¥ 4,100.00
现货

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Background

SGI-1776 free base, N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine, is a potent ATP-competitive inhibitor of the serine/threonine family of Pim kinase, an enzyme regulating cell survival. Through extensive biomedical characterization, SGI-1776 exhibits specificity to the three isoforms of the Pim family, including Pim-1, Pim-2, and Pim-3. According to preliminary results from studies treating prostate cancer cells, SGI-1776 dose-dependently reduces phosphorylation of known Pim kinase substrates involved in cell cycle progression and apotosis (p21Cip1/WAF1 and Bad), compromises overall cell viability by inducing G1 cell cycle arrest and triggering apoptosis, and reduces cell viability in a multidrug resistance 1 (MDR1) protein based taxane-refractory prostate cancer cell line.

Reference

Shannon M. Mumenthaler, Patricia Y.B. Ng, Amanda Hodge, Davide Bearss, Gregory Berk, Sarath Kanekal, Sanjeev Redkar, Pietro Taverna, Davide B. Agus, and Anjali Jain. Pharmacological inhibition of Pim kinases alters prostate cancer cell growth and resensitizes chemoresistant cells to taxanes. Mol Cancer Ther. 2009; 8(10): 2882-2893

Lisa S. Chen, S anjeev Redkar, David Bearss, William G. Wierda and Varsha Gandhi. Pim kinase inhibitor, SGI-1776, induces apoptosis in CLL lymphocytes. Blood. 2009; 114(19): 4150-4157

文献引用

1. Nurbek Mambetsariev. "Mechanisms of TRAF3 mediated regulation of B cell survival." University of Iowa.2018.
2. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
3. Winter PS, et al. "RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis." Sci Signal. 2014 Dec 23. PMID:25538080

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt405.42
Cas No.1025065-69-3
FormulaC20H22F3N5O
SynonymsSGI1776,SGI 1776
Solubility≥40.5 mg/mL in DMSO, ≥101 mg/mL in EtOH, <2.41 mg/mL in H2O
Chemical NameN-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine
SDFDownload SDF
Canonical SMILESCN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2
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

细胞实验[1]:

细胞系

CLL患者中分离的原代淋巴细胞

溶解方法

在DMSO中的溶解度>10 mM。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

10 μM;24小时

应用

原代CLL细胞与1、3和10 μM的SGI-1776孵育24小时导致细胞凋亡的增加,与未处理细胞相比,分别增加了10%、22%和38%。CLL细胞与SGI-1776孵育48或72小时进一步增加凋亡细胞的百分比。

动物实验[2]:

动物模型

786-O或Caki-1异种移植雌性BALB/c裸鼠

剂量

200 mg/kg,一次/5天,3周;口服给药

应用

与对照组相比,在两个异种移植模型中,SGI-1776显著减少平均肿瘤体积。除此之外,SGI-1776诱导Bad磷酸化的减少,而不改变总Bad蛋白的水平。SGI-1776也可以诱导适度的细胞凋亡。

注意事项

请测试所有化合物在室内的溶解度,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:

[1] Chen L S, Redkar S, Bearss D, et al. Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells. Blood, 2009, 114(19): 4150-4157.

[2] Mahalingam D, Espitia C M, Medina E C, et al. Targeting PIM kinase enhances the activity of sunitinib in renal cell carcinoma. British journal of cancer, 2011, 105(10): 1563-1573.

生物活性

描述 SGI-1776是一种新型的ATP竞争性Pim1抑制剂,IC50值为7 nM,比对Pim2和Pim3的选择性分别高50倍和10倍。
靶点 Pim1 Pim2 Pim3 FLT3    
IC50 7 nM 363 nM 69 nM 44nM    

质量控制

化学结构

SGI-1776 free base

相关生物数据

SGI-1776 free base

相关生物数据

SGI-1776 free base

相关生物数据

SGI-1776 free base