NCGC00029283 is a werner syndrome helicase-nuclease (WRN) helicase inhibitor with IC50s of 2.3 μM, 12.5 μM, and 3.4 μM for WRN, BLM and FANCJ helicase, respectively[1].
[1]. Joshua A Sommers, et al. A high-throughput screen to identify novel small molecule inhibitors of the Werner Syndrome Helicase-Nuclease (WRN). PLoS One. 2019 Jan 9;14(1):e0210525.
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[1].
体外研究 (In Vitro)
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[1]. NSC 617145 (0.75 μM; 6 hours) induces WRN binding to chromatin and proteasomal degradation[1]. 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[1]. NSC 617145, induces cell cycle arrest and apoptosis in human T-cell leukemia virus type 1 (HTLV-1)-transformed adult T-cell leukemia cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Viability Assay[1]
Cell Line:
HeLa cells
Concentration:
0.75 μM, 1 μM, 1.5 μM, 2 μM, 3 μM
Incubation Time:
24 hours, 48 hours, 72 hours
Result:
Inhibited cell proliferation in a WRN-specific manner.
Western Blot Analysis[1]
Cell Line:
HeLa cells
Concentration:
0.75 μM
Incubation Time:
6 hours
Result:
Caused WRN to become degraded by a proteasome-mediated pathway.
分子量
400.04
Formula
C13H10Cl4N2O4
CAS 号
203115-63-3
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 16.67 mg/mL (41.67 mM; ultrasonic and warming and heat to 80°C)
[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.
