DNA-PK-IN-8 is a potent, selective, and orally active inhibitor of DNA-dependent protein kinase (DNA-PK) with an IC50 value of 0.8 nM, demonstrating synergistic antiproliferative effects across various cancer cell lines and significantly reducing HL-60 tumor growth when combined with Doxorubicin [1].

DNA-PK-IN-8 (compound DK1) effectively reduces γH2A.X expression in a concentration-dependent manner in HCT-116 cells at 1, 5, and 10 μM after 6 hours of incubation, following Bleomycin pre-treatment, as confirmed by immunofluorescence analysis [1].

DNA-PK-IN-8, administered orally at a dose of 100 mg/kg daily for 16 days, significantly inhibited HL-60 tumor growth in nude mice when used in conjunction with Doxorubicin, demonstrating tumor growth inhibition (TGI) values of 52.4% and 62.4% for tumor weight and volume, respectively. Additionally, a single oral dose of DNA-PK-IN-8 at 5 mg/kg in Sprague-Dawley rats revealed favorable pharmacokinetic properties, both in vitro and in vivo, supporting its potential as an oral therapeutic candidate. The pharmacokinetic analysis in Sprague-Dawley rats showed a maximum plasma concentration (Cmax) of 810 ± 122.32 ng/mL, achieved at a median time (Tmax) of 0.42 ± 0.11 hours, with a half-life (t1/2) of 1.59 ± 0.26 hours and an area under the curve (AUC 0-∞) of 3598.7 ± 769.81 ng/mL·h, indicating its reasonable pharmacokinetic profile.