Formulation: A solid
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
Purity: ≥98%
Formula Markup: C31H31ClF3N9O5
Formula Weight: 702,1
Shelf life (days): 1460
CAS Number: 2869954-34-5
Notes: 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).{66921} 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 γ histone H2AX (γH2AX) 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.
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