NSC 15765 (Compound C5, DNA2 inhibitor C5) is an effective, selective and competitive inhibitor of DNA2 nuclease with IC50 of 20 uM.
NSC 15765 poorly inhibits the activities of the other two nucleases, FEN1 and EXO1.
NSC 15765 suppresses resection-related homology directed repair (HDR) and single-stand annealing (SSA) and causes accumulation of phosphorylated RPA foci, and inhibits restart of stalled DNA replication forks and over-resection of nascent DNA in cells defective in fork protection.
NSC 15765 exhibits cytotoxicity against a panel of 18 cell lines with IC50 of 7-70 uM.
NSC 15765 sensitizes cells to PARP inhibitor MK-4827; also sensitizes cells to CPT and synergizes with PARP inhibitors.
NSC 15765 also can mimics DNA2 knockout and synergistically kills cancer cells when combined with an ATR inhibitor.
Physicochemical Properties
M.Wt
234.167
Formula
C10H6N2O5
Appearance
Solid
CAS No.
Storage
Solide Powder
-20 °C 12 Months; 4°C 6 Months
In Solvent
-80 °C 6 Months; -20°C 6 Months
Shipping
Solubility
10 mM in DMSO
Chemical Name/SMILES
8-nitro-4-oxo-1H-quinoline-3-carboxylic acid
References
1. Liu W, et al. EBioMedicine. 2016 Apr;6:73-86.
2. Li Z, et al. EMBO J. 2018 Jul 13;37(14). pii: e96729.
