VE-822
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.
VE-822是ATR的抑制剂,IC50值为0.019 μM。VE-822是VE-821的类似物,对ATR的作用比VE-821强。
放疗(XRT)和化疗诱导染色体DNA损伤,造成的双链DNA断裂和复制压力分别诱导ATM和ATR(ATM-Rad3-related)蛋白激酶的激活。DNA损伤响应(DDR)的缺陷(例如ATM和p53 缺失/突变)在人体肿瘤中很常见,而且在胰腺癌(PDAC)病人中的比例高达70%。它们可能导致正常细胞和肿瘤细胞对DNA修复信号有不同的反应,可用于增加放化疗诱导的染色体DNA损伤对细胞的杀伤力。
在放疗处理的癌细胞中,VE-822减少细胞周期检验点,减少同源重组,增加持续性的DNA损伤。用放疗或gemcitabine处理胰腺癌细胞后,VE-822降低胰腺癌细胞而非正常细胞的存活。在放疗和基于gemcitabine的化疗之后,VE-822大大延长了胰腺癌异种移植动物中肿瘤的生长,而对正常细胞或组织没有细胞毒性。
参考文献:
1. Fokas E, Prevo R, Pollard JR et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441.
- 1. Zhengke Li, Hui Wang-Heaton, et al. "ATR prevents Ca2+ overload-induced necrotic cell death through phosphorylation-mediated inactivation of PARP1 without DNA damage signaling." FASEB J. 2021 May;35(5):e21373. PMID: 33811702
- 2. Kelli L Goss, Stacia L Koppenhafer, et al. "The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors." Oncogene. 2021 Jan;40(3):564-577. PMID: 33191406
- 3. Koppenhafer SL, Goss KL, et al. "mTORC1/2 and protein translation regulate levels of CHK1 and the sensitivity to CHK1 inhibitors in Ewing sarcoma cells." Mol Cancer Ther. 2018 Oct 3. pii: molcanther.0260.2018. PMID: 30282812
- 4. Le TM, Poddar S, Capri JR, et al. "ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways." Nat Commun. 2017 Aug 14;8(1):241. PMID: 28808226
Storage | Store at -20°C |
M.Wt | 463.55 |
Cas No. | 1232416-25-9 |
Formula | C24H25N5O3S |
Solubility | ≥50 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
Chemical Name | 3-[3-[4-(methylaminomethyl)phenyl]-1,2-oxazol-5-yl]-5-(4-propan-2-ylsulfonylphenyl)pyrazin-2-amine |
SDF | Download SDF |
Canonical SMILES | CC(C)S(=O)(=O)C1=CC=C(C=C1)C2=CN=C(C(=N2)C3=CC(=NO3)C4=CC=C(C=C4)CNC)N |
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 |
胰腺导管腺癌细胞(PDAC) |
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 |
1-2 h |
实验结果 |
VE-822降低辐射p53突变体和K-Ras突变体PDAC的存活。在化学放射治疗后,VE-822和gemcitabine的组合给药减少存活2-3倍。此外,VE-822增加辐射诱导的残余gH2AX和53BP1病灶,并减少辐射后Rad51病灶。 |
动物实验: [1] | |
动物模型 |
胰腺癌异种移植物雌性Balb/c裸鼠 |
给药剂量 |
口服,60 mg/kg |
制备方法 |
10%维生素E d-α生育酚聚乙二醇1000琥珀酸酯 |
实验结果 |
在给予DNA损伤剂后,VE-822抑制磷酸-Ser-345-Chk1。与单独的辐射相比,VE-822和辐射的组合显著延长了肿瘤生长延迟。此外,与gemcitabine+辐射的组合相比,VE-822+gemcitabine+辐射的组合组中的肿瘤生长延迟时间更长。 |
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. Fokas E, Prevo R, Pollard JR et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012 Dec 6;3:e441. |
质量控制和MSDS
- 批次: