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UMI-77

现货
Catalog No.
B4881
Mcl-1抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,150.00
现货
5mg
¥ 1,000.00
现货
25mg
¥ 3,600.00
现货

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Background

UMI-77 is a novel small-molecule inhibitor of Mcl-1 with Ki and IC50 values of 0.49 μM and 0.31 μM [1].

Myeloid cell leukemia-1 (Mcl-1) is a member of the prosurvival Bcl-2 family and is a potent anti-apoptotic protein. Mcl-1 acts as an important survival factor in a broad range of human cancers [1].

UMI-77 is a novel small-molecule Mcl-1 inhibitor. In FP-based binding assays, UMI-77 potently and selectively displaced fluorescent labeled BID-BH3 peptide from Mcl-1 protein with Ki value of 0.49μM and bound to the BH3 binding pocket of Mcl-1 protein. UMI-77 bound to A1/Bfl-1, Bcl-w, Bcl-2 and Bcl-xL with Ki values of 5.33, 8.19, 23.83 and 32.99μM. In a pull-down assay, UMI-77 at 10 μM effectively and dose-dependently inhibited the interactions between BL-Noxa and cellular Mcl-1. It was reported that Mcl-1 regulates pro-apoptotic Bax and Bak proteins and preventing their pro-apoptotic activity. UMI-77 dose-dependently inhibited the binding of Mcl-1 to Bax with IC50 value of 1.43μM. In PC cells, UMI-77 inhibited cell growth and induced apoptosis in a time and dose-dependent way [1].

In BxPC-3 xenografted SCID mice model, UMI-77 exhibited robust anti-tumor efficacy with no toxicity. Also, UMI-77 decreased the anti-apoptotic protein survivin, which potently inhibited apoptosis by antagonizing caspase activity [1].

Reference:
[1].  Abulwerdi F, Liao C, Liu M, Azmi AS, et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther, 2014, 13(3): 565-575.

文献引用

1. Robinson EJ, Aguiar SP, et al. "Survival of midbrain dopamine neurons depends on the Bcl2 factor Mcl1." Cell Death Discov. 2018 Nov 21;4:107. PMID:30479840

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt468.34
Cas No.518303-20-3
FormulaC18H14BrNO5S2
Solubility≥23.4mg/mL in DMSO
Chemical Name2-[4-[(4-bromophenyl)sulfonylamino]-1-hydroxynaphthalen-2-yl]sulfanylacetic acid
SDFDownload SDF
Canonical SMILESC1=CC=C2C(=C1)C(=CC(=C2O)SCC(=O)O)NS(=O)(=O)C3=CC=C(C=C3)Br
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

胰腺癌细胞(PC)

制备方法

溶解度有限。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。

反应条件

~24 h

实验结果

UMI-77抑制PC细胞的生长,特别是对于BxPC-3和Panc-1细胞系具有最高效力。在Panc-1细胞中,UMI-77以时间和剂量依赖性方式有效诱导凋亡。此外,它还以剂量依赖性方式诱导细胞色素c和Smac从线粒体的释放。此外,通过敲低 Mcl-1的表达可消除UMI-77的生长抑制和凋亡效应。

动物实验 [1]:

动物模型

BxPC-3异种移植物的SCID小鼠模型

给药剂量

60 mg/kg,静脉注射

实验结果

每周连续5天的UMI-77治疗两周显著抑制65%和56%肿瘤生长。与对照组相比,UMI-77显著增加肿瘤切片的阳性凋亡细胞。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Abulwerdi F, Liao C, Liu M et al. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo. Mol Cancer Ther. 2014 Mar;13(3):565-75.

质量控制

化学结构

UMI-77

相关生物数据

UMI-77