DNA-PK inhibitor NU7441 Small Molecule (Tool Compound)
- Name Bernard Golding ; Laurent Rigoreau
- Institute Newcastle University
Tool name: DNA-PK inhibitor NU7441 Small Molecule (Tool Compound)
Alternate names: DNA-dependent protein kinase (DNA-PK) inhibitor NU7441
Molecular formula: C25H19NO3S
Tool type: Small molecules
Tool sub-type: Inhibitor
Molecular weight of the target: 413.49 g/mol
Application: NU7441 intraperitoneally administrated at dose of 10 mg/kg maintains for at least 4 hours shows nontoxic and increases etoposide-induced tumor growth delay 2-fold in mice bearing SW620 xenografts. NU7441 increases the persistence of ÎłH2AX foci after ionizing radiationâinduced or etoposide-induced DNA damage. NU7441 (0.5 ÎźM or 1 ÎźM) appreciably increases G2-M accumulation induced by ionizing radiation, etoposide, and doxorubicin in both SW620 and LoVo cells. NU7441 causes persistence of doxorubicin- and ionising radiation-induced DNA double-strand break and also slightly decreases homologous recombination activity DNA-PK-proficient M059-Fus-1 and DNA-PK-deficient M059 J human tumour cells. NU7441 inhibits UV-induced RPA p34 hyperphosphorylation in a dose-dependent manner both in cells lacking and cells expressing polymerase Îˇ. NU7441 increases levels of fludarabine-induced ÎłH2AX foci and correspondingly decreased fludarabine-induced cell death in chronic lymphocytic leukemia cells. NU7441 also inhibits mitoxantrone-induced DNA-PKcs autophosphorylation and repair in chronic lymphocytic leukemia cells.
Description: NU7441 is a highly potent and selective DNA-PK inhibitor.
Research area: Cell Signaling & Signal Transduction; DNA Damage and Repair; Epigenetics & Nuclear Signalling
Selectivity: Also inhibits PI3K with IC50 of 5 ÎźM in cell-free assays.
IC50: 14 nM
- For Research Use Only
- • Zhao et al. 2006. Cancer Res. 66(10):5354-62. PMID: 16707462.
- • Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441.
- • Leahy et al. 2004. Bioorg Med Chem Lett. 14(24):6083-7. PMID: 15546735.
- • Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries.