For research use only. Not for therapeutic Use.
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].
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].
| Catalog Number | R028298 |
| CAS Number | 203115-63-3 |
| Synonyms | 3,4-dichloro-1-[3-(3,4-dichloro-2,5-dioxopyrrol-1-yl)-2,2-dimethylpropyl]pyrrole-2,5-dione |
| Molecular Formula | C13H10Cl4N2O4 |
| Purity | ≥95% |
| InChI | InChI=1S/C13H10Cl4N2O4/c1-13(2,3-18-9(20)5(14)6(15)10(18)21)4-19-11(22)7(16)8(17)12(19)23/h3-4H2,1-2H3 |
| InChIKey | PCOXPBOKDABARQ-UHFFFAOYSA-N |
| SMILES | CC(C)(CN1C(=O)C(=C(C1=O)Cl)Cl)CN2C(=O)C(=C(C2=O)Cl)Cl |
| Reference | [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. |
