Sigma-Aldrich Ikke/Tbk1 Inhibitor Ii Mrt

Assay

≥95% (HPLC)

Quality Level

100

Form

solid

Manufacturer/Tradename

Calbiochem^®

Storage Condition

OK to freeze
protect from light

Color

amber

Solubility

DMSO: 100 mg/mL

Storage Temp.

2-8°C

Inchi

1S/C26H36N6O2/c33-25(21-5-2-6-21)28-11-3-10-27-24-23(20-8-9-20)17-29-26(31-24)30-22-7-1-4-19(16-22)18-32-12-14-34-15-13-32/h1,4,7,16-17,20-21H,2-3,5-6,8-15,18H2,(H,28,33)(H2,27,29,30,31)

Inchi Key

UKBGBACORPRCGG-UHFFFAOYSA-N

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.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: yesPrimary Target
TBK1 kinase dimer interfaceReversible: yesSecondary Target
IKKe, MARK, SIK

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Other Notes

Bruni, D., et Al. 2013.J. Immunol. 190,2844.
Tu, D., et Al.Cell Reports 3,747.
Larabi, A., et Al.Cell Reports 3,734.
Clark, K., et Al. 2012.Proc. Natl. Acad. Sci. USA 109,16986.
Clark, K., et Al. 2011.Proc. Natl. Acad. Sci. USA 108,17093.
Clark, K., et Al. 2011.Biochem. J. 434,93.CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany