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LDC000067

现货
Catalog No.
B4754
高特异性的CDK9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
10mg
¥ 950.00
现货
50mg
¥ 3,830.00
现货

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Background

LDC000067 (LDC067) is a novel specific inhibitor of CDK9 with IC50 value of 44 ± 10 nM [1].

Cyclin-dependent kinase 9 (CDK9) is a cyclin-dependent kinase. CDK9 and cyclin T form the positive transcription elongation factor b (P-TEFb) complex for RNA polymerase II and functions by phosphorylating the C-terminal domain of the largest subunit of RNA polymerase II [1].

LDC000067 (LDC067) is a novel and highly specific CDK9 inhibitor. LDC000067 exhibited selectivity for CDK9 over other CDKs in the range of 55-fold (vs. CDK2) to over 230-fold (vs. CDK6 and CDK7). LDC067 also inhibited transcription in a dose-dependent and ATP-competitive manner. In whole cells, LDC000067 induced the tumor suppressor protein p53 activation and apoptosis. LDC000067 also selectively reduced short-lived mRNAs, including those that encode regulators of apoptosis and proliferation such as MYC and MCL1 [1].

Reference:
[1].  Albert TK, Rigault C, Eickhoff J, et al. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. Br J Pharmacol, 2014, 171(1): 55-68.

文献引用

1. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID:29507054
2. Yuan J, Jiang YY, et al. "Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma." Cancer Res. 2017 Dec 1;77(23):6614-6626. PMID:28951465

Chemical Properties

StorageDesiccate at -20°C
M.Wt370.43
Cas No.1073485-20-7
FormulaC18H18N4O3S
Solubility≥18.52mg/mL in DMSO
Chemical Name(3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methanesulfonamide
SDFDownload SDF
Canonical SMILESCOC1=CC=CC=C1C2=CC(NC3=CC=CC(CS(N)(=O)=O)=C3)=NC=N2
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]:

抑制活性

在无线测量实验中测量LDC000067的激酶抑制,其直接测量对特定底物的激酶催化活性。简言之,将10 μM LDC000067或作为溶剂对照的DMSO加入到碱性反应缓冲液(10 mM MgCl2、1 mM EDTA、20 mM HEPES、pH 7.5、2 mM DTT、0.02mg/mL BSA、0.1 mM Na3VO4、0.02% Brij35、1% DMSO),其含有个别激酶所需的辅因子和底物。向反应混合物中加入10μCi的[γ-33P]-APP(10mCi·mL-1, 3000Ci·mmol-1, Perkin Elmer)。在室温下孵育120分钟进行激酶反应。在P81离子交换纸上发生反应,通常在放射性定量之前用0.75%磷酸洗涤滤器。每个蛋白激酶测量一式两份,其催化活性表示为残余激酶活性,其显示与溶剂对照反应相比的平均底物磷酸化的百分比。

细胞实验 [1]:

细胞系

HEK293T细胞、THP1细胞

制备方法

该化合物在DMSO中的溶解度大于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。

反应条件

竞争激酶结合替换实验:90分钟。DNA微阵列分析实验:90分钟。

实验结果

tors of proliferation and apoptosis, such as MCL1 and MYC.LDC000067抑制CDK9,IC50值为44 nM,其对CDK9的选择性高于其他CDKs 55倍甚至超过230倍,特别是在ATP竞争性激酶结合实验中显示出更高的选择性。此外,在全细胞中,LDC000067的效应包括诱导肿瘤抑制蛋白p53和诱导细胞凋亡。此外,LDC000067处理细胞的基因表达谱表明,编码增殖和凋亡调节剂如MCL1和MYC的短寿命mRNA选择性下降。

References:

[1]. T K Albert1, C Rigault1, J Eickhoff, K Baumgart, C Antrecht1, B Klebl, G Mittler and M Meisterernst. Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor. British Journal of Pharmacology. 2014, 171: 55–68.

生物活性

描述 LDC000067是一种高选择性的CDK9抑制剂,IC50值为44 nM。
靶点 CDK9          
IC50 44 nM          

质量控制

化学结构

LDC000067

相关生物数据

LDC000067

相关生物数据

LDC000067