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NSC 617145

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Chemical Structure| 203115-63-3 同义名 : -
CAS号 : 203115-63-3
货号 : A533499
分子式 : C13H10Cl4N2O4
纯度 : 98%+
分子量 : 400.041
MDL号 : MFCD28100812
存储条件:

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 9 mg/mL(22.5 mM),配合低频超声,并水浴加热至45℃助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:
生物活性
描述 The Werner syndrome helicase (WRN) is an ATP-dependent helicase with 3' to 5' DNA exonuclease activity that regulates the replicative potential of dividing cells, and WRN loss-of-function mutations promote cellular senescence and neoplastic transformation[2]. WRN helicase has several roles in genome maintenance, such as replication, base excision repair, recombination, DNA damage response and transcription. These processes are often found upregulated in human cancers, many of which display increased levels of WRN[3]. WRN depletion in HeLa cells attenuates global protein synthesis without affecting the level of key components of the mRNA export machinery. WRN depletion affects the nuclear export of mRNAs and demonstrated that WRN interacts with mRNA and the Nuclear RNA Export Factor 1 (NXF1)[4]. NSC617145 is a WRN helicase inhibitor. In FA-D2(-/-) cells, NSC 617145 acted synergistically with very low concentrations of mitomycin C to inhibit proliferation in a WRN-dependent manner and induce double-strand breaks (DSB) and chromosomal abnormalities. Under these conditions, ataxia-telangiectasia mutated activation and accumulation of DNA-dependent protein kinase, catalytic subunit pS2056 foci suggested an increased number of DSBs processed by nonhomologous end-joining (NHEJ). Rad51 foci were also elevated in FA-D2(-/-) cells exposed to NSC 617145 and mitomycin C, suggesting that WRN helicase inhibition interferes with later steps of homologous recombination at ICL-induced DSBs[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.50mL

0.50mL

0.25mL

12.50mL

2.50mL

1.25mL

25.00mL

5.00mL

2.50mL

参考文献

[1]Aggarwal M, Banerjee T, Sommers JA, Iannascoli C, Pichierri P, Shoemaker RH, Brosh RM Jr. Werner syndrome helicase has a critical role in DNA damage responses in the absence of a functional fanconi anemia pathway. Cancer Res. 2013 Sep 1;73(17):5497-507. doi: 10.1158/0008-5472.CAN-12-2975. Epub 2013 Jul 18. PMID: 23867477; PMCID: PMC3766423.

[2] Stephen G Chun,et al. The Werner's Syndrome RecQ helicase/exonuclease at the nexus of cancer and aging. Hawaii Med J. 2011 Mar;70(3):52-5.

[3]Natalie Orlovetskie,et al. Targeted inhibition of WRN helicase, replication stress and cancer. Biochim Biophys Acta Rev Cancer. 2017 Jan;1867(1):42-48.

[4]Juan Manuel Iglesias-Pedraz,et al. WRN modulates translation by influencing nuclear mRNA export in HeLa cancer cells. BMC Mol Cell Biol. 2020 Oct 14;21(1):71.

[5]Monika Aggarwal,et al. Werner syndrome helicase has a critical role in DNA damage responses in the absence of a functional fanconi anemia pathway. Cancer Res. 2013 Sep 1;73(17):5497-507.