In Vitro: NU7026 (10 μM) potentiates ionizing radiation (IR) cytotoxicity [potentiation factor at 90% cell kill (PF90)=1.51±0.04] in exponentially growing DNA-PK proficient but not deficient cells. NU7026 synergistically sensitizes I83 cells to Chlorambucil (CLB) 3.5-fold.NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 μM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. ?Solutionin vitro: NU7026 is dissolved in anhydrous DMSO. NU7026 is added to cells to a final concentration of 0.25% DMSO (v/v).
In Vivo: NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Following intravenous administration to mice at 5 mg/kg, NU7026 underwent rapid plasma clearance (0.108 L/h) and this is largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg/kg is 20 and 15%, respectively. ?Solution in vivo: ?NU7026 is formulated in 10% DMSO and 5% Tween 20 in saline (i.p. and p.o.) (Mice). ?NU7026 is formulated in 10% ethanol, 25% PEG 200 and 5% Tween 20 in saline (i.v.).