SGI-1776 free base
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
SGI-1776 free base是一种有效的ATP竞争性Pim激酶抑制剂。Pim激酶属于丝氨酸/苏氨酸激酶家族，调节细胞存活。生物医学鉴定表明SGI-1776对Pim家族的三个亚型具有特异性，包括Pim-1、Pim-2和Pim-3。在前列腺癌细胞中，SGI-1776剂量依赖性地减少参与细胞周期进程和凋亡（p21Cip1/WAF1和Bad）的Pim激酶底物的磷酸化；通过诱导G1细胞周期停滞损害整体细胞活力，触发凋亡；降低基于多药耐药蛋白1（MDR1）的紫杉醇难治的前列腺癌细胞的细胞活力。
参考文献：
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
- 1. Whillock AL, Mambetsariev N, et al. "TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells." Sci Rep. 2019 Sep 9;9(1):12884. PMID:31501481
- 2. Nurbek Mambetsariev. "Mechanisms of TRAF3 mediated regulation of B cell survival." University of Iowa.2018.
- 3. Kris Cameron Wood,Peter Saville Winter. "Compositions and Methods for Treating Cancer with JAK2 Activity." US Patent App. 15/027,216, 2016.
- 4. Winter PS, et al. "RAS signaling promotes resistance to JAK inhibitors by suppressing BAD-mediated apoptosis." Sci Signal. 2014 Dec 23. PMID:25538080
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 405.42 |
| Cas No. | 1025065-69-3 |
| Formula | C20H22F3N5O |
| Synonyms | SGI1776,SGI 1776 |
| Solubility | ≥40.5 mg/mL in DMSO; insoluble in H2O; ≥101 mg/mL in EtOH |
| Chemical Name | N-[(1-methylpiperidin-4-yl)methyl]-3-[3-(trifluoromethoxy)phenyl]imidazo[1,2-b]pyridazin-6-amine |
| SDF | Download SDF |
| Canonical SMILES | CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 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。溶液形式一般不宜长期储存，请尽快用完。 |
| 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. |
|
| 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 | ||
质量控制和MSDS
- 批次：
化学结构
相关生物数据
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