JAK2-IN-7, a selective inhibitor targeting Janus Kinase 2 (JAK2), exhibits inhibitory concentrations (IC50) of 3 nM for JAK2, 11.7 nM for SET-2 cells, and 41 nM for Ba/F3 V617F cells, indicative of its potency and selectivity. This compound demonstrates more than 14-fold selectivity against JAK1, JAK3, and FLT3, underlining its specificity. JAK2-IN-7 effectively induces cell cycle arrest at the G0/G1 phase and promotes apoptosis in tumor cells, manifesting significant antitumor activities [1].

JAK2-IN-7 (compound 13ac), in concentrations ranging from 0-1000 nM for 2 hours, dose-dependently inhibits the phosphorylation of JAK2 and STAT5 in both SET-2 and Ba/F3-JAK2 V617F cells. Additionally, at 10-160 nM over 24 hours, it promotes cell cycle arrest at the G0/G1 phase, and at 0.05-1.6 μM for 2 hours, it induces apoptosis in SET-2 cells. Both the cell cycle arrest and apoptosis induction are concentration-dependent, confirming the compound's efficacy in modulating key cellular processes related to proliferation and survival.

JAK2-IN-7, administered orally at doses ranging from 15 to 60 mg/kg daily for 16 days, demonstrated strong antitumor activity, inhibiting tumor growth by 82.3% in the SET-2 xenograft model [1]. At doses between 30 and 60 mg/kg, it significantly reduced disease symptoms in a Ba/F3-JAK2V617F allograft model by normalizing spleen weight by 77.1%, outperforming Ruxolitinib [1]. These findings, derived from administering JAK2-IN-7 to a NOD/SCID mouse model inoculated with SET-2 cells, highlight its potential without noticeable weight changes in the animals.