A cell-permeable BX795 analog that acts as a potent, ATP-competitive, and reversible dual kinase inhibitor of TBK1/IKK epsilon (IC50 = 19 and 160nM, respectively) with excellent selectivity over IKKalpha and IKKbeta (IC50 > 10uM). Interacts with the TBK1 kinase dimer interface and stabilizes the inactive DFG-out conformation. Also blocks the activity of MARK (microtubule- associated protein (MAP)-microtubule affinity regulating kinase) 1, 2, 3, and 4 (IC50 = 27, 52, 36, and 41nM, respectively), SIK2 (IC50 = 67nM) and Aurora B, JAK2, and MLK1,3 (> than 90% inhibition at 1uM) in a 108-kinase panel. Increases TNF-alpha-stimulated NF-kB-dependent gene transcription in wild-type macrophages and enhances CREB-dependent gene transcription by promoting dephosphorylation of CREB-regulated transcription coactivator (CRTC3). Shown to aid TLR-stimulated production of anti-Inflammatory cytokines in macrophages while suppressing the secretion of pro-inflammatory cytokines. In response to pro-inflammatory stimuli, pre-treatment of BX795 robustly suppresses the activation of JNK and p38alpha, whereas MRT67307 does not exhibit such off-target effects.
Please note that the molecular weight for this compound is batch-specific due to variable water content.
Molecular Formula:C₂₆H₃₆N₆O₂
Solubility:DMSO
Primary Target:TBK1 kinase dimer interface
Secondary Target:IKKe, MARK, SIK
Storage and Stability:May be stored at 4°C. For long-term storage, aliquot and store at 4°C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.
