| 靶点: |
NSC 617145 is a selective werner syndrome helicase (WRN) helicase inhibitor with an IC50 value of 230 nM. NSC 617145 inhibits WRN ATPase, and induces double-strand breaks (DSB) and chromosomal abnormalities. NSC 617145 shows selective for WRN over BLM, FANCJ, ChlR1, RecQ, and UvrD helicases. |
| 体外研究: |
NSC 617145 (0.75-3 μM; 24-72 hours) shows maximal inhibition of proliferation (98%) at the lowest concentration in a WRN-specific manner in HeLa cells. NSC 617145 (0.75 μM; 6 hours) induces WRN binding to chromatin and proteasomal degradation. In FA-D2-/- cells, NSC 617145 (0.125 μM) acts 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. NSC 617145 exposure results in enhanced accumulation of DNA-PKcs pS2056 foci and Rad51 foci in Mitomycin C-treated FA-deficient cells, suggesting that WRN helicase inhibition prevents processing of Rad51-mediated recombination products and activates NHEJ. NSC 617145, induces cell cycle arrest and apoptosis in human T-cell leukemia virus type 1 (HTLV-1)-transformed adult T-cell leukemia cells. |
| 参考文献: |
[1]. 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. [2]. R Moles, et al. WRN-targeted therapy using inhibitors NSC 19630 and NSC 617145 induce apoptosis in HTLV-1-transformed adult T-cell leukemia cells. J Hematol Oncol. 2016 Nov 9;9(1):121. |
| 溶解性: |
soluble in DMSO |
| 保存条件: |
-80℃(运输条件:冰袋低温运输) |
| 配置溶液浓度参考: |
|
1mg |
5mg |
10mg |
| 1 mM |
2.5 ml |
12.499 ml |
24.997 ml |
| 5 mM |
0.5 ml |
2.5 ml |
4.999 ml |
| 10 mM |
0.25 ml |
1.25 ml |
2.5 ml |
| 50 mM |
0.05 ml |
0.25 ml |
0.5 ml |
|
| 注意: |
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