Merck, 5063060001, IKKε/TBK1 Inhibitor II, MRT67307

General description
A cell-permeable BX795 analog (>Cat. No. 204001) that acts as a potent, ATP-competitive, and reversible dual kinase inhibitor of TBK1/IKKε (IC₅₀ = 19 and 160 nM, respectively) with excellent selectivity over IKKα and IKKβ (IC₅₀ >10 µM). 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 41 nM, respectively), SIK2 (IC₅₀ = 67 nM) and Aurora B, JAK2, and MLK1,3 (> than 90% inhibition at 1 µM) in a 108-kinase panel. Increases TNF-α-stimulated NF-κB-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 p38α, 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. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water and salt.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
TBK1 kinase dimer interface
Reversible: yes
Secondary Target
IKKe, MARK, SIK
Packaging
Packaged under inert gas
Other Notes
Bruni, D., et al. 2013. J. Immunol.190, 2844.
Tu, D., et al. Cell Reports3, 747.
Larabi, A., et al. Cell Reports3, 734.
Clark, K., et al. 2012. Proc. Natl. Acad. Sci. USA109, 16986.
Clark, K., et al. 2011. Proc. Natl. Acad. Sci. USA108, 17093.
Clark, K., et al. 2011. Biochem. J.434, 93.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)