T24308 |
NSC 617145 |
源叶(MedMol) | 98% |
- 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.;DNA/RNASynthesis
- 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: -20°C
- 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
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