Werner Syndrome RecQ Helicase-IN-1

An inhibitor of WRN (IC50 = 100 nM in an enzyme activity assay); selectively inhibits WRN over BLM, RecQ1, and RecQ5 (IC50s = >100 µM for all in enzyme activity assays) and the growth of SW480 cells with unstable microsatellites over CAL-33 cells with stable microsatellites (GI50s = of 0.04 and >10 µM, respectively); induces proteosomal degradation of WRN in RKO cells at 0.75-10 µM; induces cell cycle arrest at the G2 phase in HCT116 cells at 10 µM; increases the levels of γH2AX and p21 and the levels of phosphorylated ATR, Chk2, and ATM, markers of DNA damage, in HCT116 and LS411N cells at 1 or 5 µM; decreases tumor volume without reducing body weight in a SW480 mouse xenograft model at 40, 60, or 120 mg/kg per day