TBK1/IKKε-IN-4, a 6-aminopyrazolopyrimidine derivative, serves as a potent, selective inhibitor for TBK1 and IKKε, demonstrating IC50 values of 13 nM and 59 nM, respectively. This compound exhibits significantly reduced activity, by 100- to 1000-fold, against other protein kinases, such as PDK1, PI3K family members, and mTOR[1].

TBK1:13 nM (IC50), IKKε:59 nM (IC50)

TBK1/IKKε-IN-4 (Compound II; 96 hours; A549 and HCC44 cells) demonstrates selective toxicity in TBK1-dependent cancer cell lines (IC50 of ~4.2 μM for H441 cells and IC50 of ~0.4 μM for A549 cells)[1]. TBK1/IKKε-IN-4 (Compound II; 0-2 μM; 30 minutes; HCC44 cells) inhibits AKT activity[1]. TBK1/IKKε-IN-4 (Compound II) inhibits LPS-induced expression of IFNβ (IC50 = 62 nM) and the IFNβ target genes IP10 (IC50 = 78 nM) and Mx1 (IC50 = 20 nM). It effectively blocks TLR3-dependent IRF3 nuclear translocation (IC50 < 100 nM) without impairing TNFR1-dependent p65 NFκB nuclear translocation at doses up to 20 μM[1].