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

DNA-PK-IN-8 (compound DK1) decreases the expression levels of γH2A.X in a concentration-dependent manner in HCT-116 cells [1]. Immunofluorescence Cell Line: HCT-116 (treated with Bleomycin for 6 hours) [1] Concentration: 1, 5, and 10 μM Incubation Time: 6 hours Result: Decreased the expression levels of γH2A.X in a concentration-dependent manner.

DNA-PK-IN-8 (100 mg/kg; PO; QD for 16 days) significantly suppresses HL-60 tumor growth when co-administrating with Doxorubicin [1]. DNA-PK-IN-8 (5 mg/kg; PO; single dosage) exhibits reasonable pharmacokinetic properties in vitro and in vivo as an oral drug candidate [1]. Pharmacokinetic Parameters of DNA-PK-IN-8 in Sprague-Dawley rats [1]. PO (5 mg/kg) T max (h) 0.42 ± 0.11 t 1/2 (h) 1.59 ± 0.26 C max (ng/mL) 810 ± 122.32 AUC 0-∞ (ng/mL·h) 3598.7 ± 769.81 MRT 0-∞ (h) 2.29 ± 0.18 Animal Model: HL-60 tumor-bearing nude mice model [1] Dosage: 100 mg/kg Administration: PO; QD for 16 days Result: Led to significant tumor-suppressing effects with TGI values of 52.4% and 62.4% for tumor weight and tumor volume, respectively, when co-administrated with Doxorubicin. Animal Model: Sprague-Dawley rats [1] Dosage: 5 mg/kg Administration: PO; single dosage (Pharmacokinetic Analysis) Result: Exhibited reasonable pharmacokinetic properties in vitro and in vivo as an oral drug candidate.