CK2 Inhibitor 2, characterized as a potent, selective, and orally active inhibitor of CK2, demonstrates an impressive IC50 value of 0.66 nM. It exhibits high selectivity towards Clk2 with an IC50 of 32.69 nM in comparison to CK2. Furthermore, CK2 Inhibitor 2 has been shown to possess promising antiproliferative and antitumor activities [1].

CK2 inhibitor 2 (compound 1c) effectively inhibits the proliferation of various cancer cell lines including PC-3, HCT-116, MCF-7, HT-29, T24, and LO2, with IC50 values of 4.53 μM, 3.07 μM, 7.50 μM, 5.18 μM, 6.10 μM, and 96.68 μM, respectively. Additionally, it induces apoptosis in HCT-116 cells in a dose-dependent manner with a notable apoptotic ratio of about 55% at 20 μM concentration after 24 hours. It also significantly reduces the expression of phosphorylated Akt1 S129 and Cdc37 S13 in HCT-116 cells, suggesting a mechanism involving the suppression of survival pathways. Furthermore, CK2 inhibitor 2 dose-dependently inhibits ALDH1A1 enzyme activity (IC50 of 0.10 μM) and downregulates its transcription and protein expression in HCT-116 cells, highlighting its potential in targeting cancer-specific metabolic pathways.

Administering CK2 inhibitor 2 at doses ranging from 60 to 90 mg/kg orally, twice daily for four weeks, significantly inhibits tumor growth in a dose-dependent manner, achieving a peak inhibition rate of 69% at the 90 mg/kg dosage. A single oral dose of 25 mg/kg in Sprague-Dawley rats reveals pharmacokinetic parameters such as a maximum concentration (C max) of 7017.8 ng/mL, an elimination half-life (t 1/2) of 6.67 hours, and a clearance rate (CL) of 0.60 L/h/kg. The study utilized male BALB/c athymic nude mice, aged 5 weeks and weighing 16-18 grams, injected with HCT-116 cells, demonstrating dose-dependent tumor growth inhibition without noticeable changes in body weight.