TBK1/IKKε-IN-4

TBK1/IKKε-IN-4 is a 6-aminopyrazolopyrimidine derivative and a potent, selective TBK1 and IKKε inhibitor with IC₅₀ values of 13 nM and 59 nM, respectively. TBK1/IKKε-IN-4 shows 100- to 1000-fold less activity against other protein kinases including PDK1, PI3K family members and mTOR^[1]. In Vitro: TBK1/IKKε-IN-4 (Compound II; 96 hours; A549 andHCC44 cells) treatmentdisplays 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) treatment inhibits the 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). TBK1/IKKε-IN-4 effectively blocksTLR3-dependent IRF3 nuclear translocation in cells with an IC₅₀ under 100 nM, but does not impair TNFR1-dependent p65 NFκB nuclear translocation with doses as high as 20 µM^[1].