PHA-767491
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mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
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Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
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Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
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Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
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SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
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Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
PHA-767491是CDC7激酶的小分子抑制剂,IC50为10 nM [1]。
在DNA合成过程中,CDC7激酶对复制起点的活化至关重要。它磷酸化微型染色体维持蛋白(MCMS)的几个亚基,特别是MCM2 的Ser40和Ser53位点,这两个位点构成DNA复制的解旋酶。在肿瘤细胞和肿瘤标本中,CDC7过表达,因此CDC7抑制剂被开发为抗癌剂。PHA-767491作为一种小分子CDC7抑制剂,与其它靶向DNA复制的药物不同,它采取不同的机制产生抗肿瘤活性。PHA-767491与ATP竞争结合CDC7,在1.5 μM ATP存在下,IC50为10 nM [1]。
PHA-767491是选择性抑制剂。对38个丝氨酸/苏氨酸和酪氨酸激酶进行测试,它对其中的15种激酶无抑制作用。它对CDK1、CDK2和GSK-3β抑制效能低20倍。除此之外,PHA-767491对CDK9的抑制IC50为34 nM,这使得它被视为CDK7 / 9激酶双重抑制剂。使用PHA-767491处理61种人细胞系,可以抑制细胞增殖,平均IC50为3.17 μM。它可以杀死p53阳性和p53阴性的细胞。但是,NHDF和MCF7细胞对PHA-767491具有抗性。K562细胞对PHA-767491不敏感[1]。
在HL60细胞系肿瘤异种移植小鼠中,给药PHA-767491剂量20和30 mg/kg,每天两次,剂量依赖性的减少肿瘤体积。在A2780卵巢癌、HCT-116结肠癌或MX-1乳腺腺癌异种移植模型中,PHA-767491导致50%的肿瘤生长抑制[1]。
参考文献:
[1] Montagnoli A, Valsasina B, Croci V, et al. A Cdc7 kinase inhibitor restricts initiation of DNA replication and has antitumor activity. Nature chemical biology, 2008, 4(6): 357-365.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 213.24 |
Cas No. | 845714-00-3 |
Formula | C12H11N3O |
Synonyms | CAY10572;PHA767491;PHA 767491;CAY-10572;CAY 10572 |
Solubility | insoluble in H2O; insoluble in EtOH; ≥10.65 mg/mL in DMSO |
Chemical Name | 2-pyridin-4-yl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one |
SDF | Download SDF |
Canonical SMILES | C1CNC(=O)C2=C1NC(=C2)C3=CC=NC=C3 |
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。 |
Description | PHA-767491是CDC7和CDK9的强效ATP竞争性抑制剂,IC50分别为10 nM和34 nM。 | |||||
靶点 | cdc7 | cdk9 | ||||
IC50 | 10 nM | 34 nM |
质量控制和MSDS
- 批次:
化学结构
![PHA-767491](http://www.apexbt.com//media/diy/images/struct/A3721.png)