您好,欢迎来到试剂信息网! [登录] [免费注册]
试剂信息网
位置:首页 > 产品库 > UM-164
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
UM-164
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
UM-164图片
CAS NO:903564-48-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 640.69
Formula C30H31F3N8O3S
CAS No. 903564-48-7
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10mM
Water:
Ethanol:
Chemical Name 2-[[6-[4-(2-Hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-N-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]-5-thiazolecarboxamide
Synonyms UM-164; UM 164; UM164
SMILES Code O=C(C1=CN=C(NC2=NC(C)=NC(N3CCN(CCO)CC3)=C2)S1)NC4=CC(NC(C5=CC=CC(C(F)(F)F)=C5)=O) =CC=C4C
实验参考方法
In Vitro

In vitro activity: UM-164 is a potent Src/p38 inhibitor with potential anticancer activity for Triple-Negative Breast Cancer (TNBC). It is a promising lead compound for developing the first targeted therapeutic strategy against TNBC. c-Src has been shown to play a pivotal role in breast cancer progression, metastasis, and angiogenesis. In the clinic, however, the limited efficacy and high toxicity of existing c-Src inhibitors have tempered the enthusiasm for targeting c-Src. UM-164 binds the inactive kinase conformation of c-Src. Kinome-wide profiling of UM-164 identified that Src and p38 kinase families were potently inhibited by UM-164. UM-164 alters the cell localization of c-Src in TNBC cells. In xenograft models of TNBC, UM-164 resulted in a significant decrease of tumor growth compared with controls, with limited in vivo toxicity.


Kinase Assay: UM-164 is a potent and dual inhibitor of the Src/p38 kinase with potential anticancer activity. UM-164 binds the inactive kinase conformation of c-Src. Kinome-wide profiling of UM-164 identified that Src and p38 kinase families were potently inhibited by UM-164.


Cell Assay: MDA-MB 468 cells were trypsinized and allowed to adhere overnight to #1.5 cover glass in a 6-well plate. Cells were then treated with 5 μmol/L dasatinib, 5 μmol/L UM-164, or vehicle (DMSO) for 4 hours. Cells were then fixed with 4% paraformaldehyde for 15 minutes at room temperature followed by three washes with PBS. The fixed cells were treated with 1 μmol/L of an irreversible turn-on Src fluorophore for 1 hour followed by three washes with PBS. Cells were then mounted on slides with UltraCruz Hard-set Mounting Medium w/DAPI (Santa Cruz Biotechnology; sc-359850) and stored for 30 minutes at 4°C in the dark.

In VivoIn xenograft models of TNBC, UM-164 resulted in a significant decrease of tumor growth compared with controls, with limited in vivo toxicity.
Animal model NCr/nude mice, 6 weeks of age
Formulation & Dosage Dissolved in a mixture of DMSO/propylene glycol (1:9); 10 mg/kg, 15 mg/kg, or 20 mg/kg; i.p. injection
References Appl Biochem Biotechnol. 2018 Jul;185(3):655-675; Clin Cancer Res. 2016 Oct 15;22(20):5087-5096; Mol Biosyst. 2017 May 30;13(6):1157-1171.
生物活性


Chemical structures of dasatinib and UM-164. A, UM-164 is a dasatinib analogue with an appended trifluoromethyl amide group (colored red) that causes binding to the inactive conformation of c-Src. B and C, MDA-MB 231 and SUM 149 cells were treated with UM-164 for 15, 30, 60, and 120 minutes at the indicated concentrations, and the whole-cell lysate was probed for P-Src/Tyr-419. Clin Cancer Res. 2016 Oct 15;22(20):5087-5096.



Inhibition of multiple signaling pathways by UM-164 and dasatinib in TNBC cell lines. Cells were treated with an increasing concentration of either UM-164 or dasatinib for 1 hour. Whole-cell lysates were collected and analyzed for the phospho-specific antibody of the indicated proteins, followed by immunoblotting for the corresponding total protein. A, SUM 149. B, MDA-MB 231. C, VARI-068, a TNBC cell line grown from a PDX. Clin Cancer Res. 2016 Oct 15;22(20):5087-5096.


Altered localization of c-Src when bound by UM-164. Representative fluorescence microscopy images of MDA-MB 468 cells treated with vehicle (DMSO), 5 μmol/L dasatinib, or 5 μmol/L UM-164 for 4 hours. In the vehicle-treated cells, c-Src (green) is predominately localized to the cell membranes. UM-164–treated cells show cytoplasmic punctate structures indicated by the white triangles. Nuclei are stained in blue (DAPI). Scale bar, 20 μm. Clin Cancer Res. 2016 Oct 15;22(20):5087-5096.


UM-164 treatment inhibits cell motility and invasion through c-Src–mediated FAK activation. Clin Cancer Res. 2016 Oct 15;22(20):5087-5096.


MDA-MB 231 and SUM 149 xenograft models. Clin Cancer Res. 2016 Oct 15;22(20):5087-5096.