NSC 617145

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]. 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].