TBK1/IKKε-IN-4 是一种 6-氨基吡唑并嘧啶衍生物，也是一种有效的，选择性的 TBK1 和 IKKε 抑制剂，IC50 值分别为 13 nM 和 59 nM。TBK1/IKKε-IN-4 对其他蛋白质激酶（包括 PDK1，PI3K 家族成员和 mTOR）的活性降低了 100-1000 倍。
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].
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].
[1]. Ou YH, et al. TBK1 directly engages Akt/PKB survival signaling to support oncogenic transformation. Mol Cell. 2011 Feb 18;41(4):458-70.
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