Werner Syndrome RecQ Helicase-IN-1

Werner syndrome RecQ helicase-IN-1 is an inhibitor of the DNA helicase Werner syndrome protein (WRN, IC50 = 100 nM in an enzyme activity assay). It selectively inhibits WRN over the DNA helicases Bloom syndrome protein (BLM), RecQ1, and RecQ5 (IC50s = >100 µM for all in enzyme activity assays) and the growth of SW480 colorectal cancer cells with unstable microsatellites over CAL-33 tongue squamous cell carcinoma cells with stable microsatellites (GI50s = 0.04 and >10 µM, respectively). Werner syndrome RecQ helicase-IN-1 (0.75-10 µM) induces proteosomal degradation of WRN in RKO colon cancer cells. It induces cell cycle arrest at the G2 phase in HCT116 colorectal cancer cells when used at a concentration of 10 µM. Werner syndrome RecQ helicase-IN-1 (1 or 5 µM) increases the levels of gamma histone H2AX (gammaH2AX) and p21 and the levels of phosphorylated ataxia-telangiectasia and Rad3-related protein/kinase (ATR), checkpoint kinase 2 (Chk2), and ataxia mutated kinase (ATM), markers of DNA damage, in HCT116 and LS411N colorectal cancer cells. In vivo, Werner syndrome RecQ helicase-IN-1 (40, 60, or 120 mg/kg per day) decreases tumor volume without reducing body weight in an SW480 mouse xenograft model.Formal Name: N-[2-chloro-4-(trifluoromethyl)phenyl]-2-(3,6-dihydro-2H-pyran-4-yl)-5-ethyl-6-[4-[(5-hydroxy-6-methyl-4-pyrimidinyl)carbonyl]-1-piperazinyl]-7-oxo-[1,2,4]triazolo[1,5-a]pyrimidine-4(7H)-acetamide. CAS Number: 2869954-34-5. Synonyms: HRO761, Werner Syndrome RecQ Helicase Inhibitor 1, WS RecQ Helicase-IN-1, WS RecQ Helicase Inhibitor 1. Molecular Formula: C31H31ClF3N9O5. Formula Weight: 702.1. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Slightly soluble: 0.1-1 mg/ml. SMILES: ClC1=CC(C(F)(F)F)=CC=C1NC(CN(C2=NC(C3=CCOCC3)=NN24)C(CC)=C(N5CCN(C(C6=NC=NC(C)=C6O)=O)CC5)C4=O)=O. InChi Code: InChI=1S/C31H31ClF3N9O5/c1-3-22-25(41-8-10-42(11-9-41)28(47)24-26(46)17(2)36-16-37-24)29(48)44-30(39-27(40-44)18-6-12-49-13-7-18)43(22)15-23(45)38-21-5-4-19(14-20(21)32)31(33,34)35/h4-6,14,16,46H,3,7-13,15H2,1-2H3,(H,38,45). InChi Key: XKYVECRUZPCRQR-UHFFFAOYSA-N.