MRT67307

TBK1/IKKε inhibitor

TBK1/IKKε signaling inhibition by MRT67307

MRT67307 is a potent, reversible kinase inhibitor specifically blocking the function of TBK1 (TANK-binding kinase 1) and I-kappa-B kinase (IKK) epsilon (IKKε, or IKBKE), thereby preventing the phosphorylation of IRF3 (interferon regulatory factor 3) and subsequent expression of interferon-stimulated genes (ISGs)  [1]. Unlike BX795 from which it is derived, MRT67307 has no noted effect on the canonical IKKs, IKKα, or IKKβ, that are involved in the activation of NF-κB [1]. Additionally, MRT67307 is a highly potent inhibitor of ULK1, a key component of the autophagy pathway [2].
 

Key features:

• MRT67307 potently inhibits IRF signaling in a dose-dependent manner.
• MRT67307 does not affect NF-κB signaling.
• InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested.

References:

1. Clark, K. et al., 2011. Novel cross-talk within the IKK family controls innate immunity. Biochem J 434, 93-104.
2. Petherick, K.J. et al., 2015. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem 290, 11376-11383.

Figures

2x10⁵ THP1-Dual™ cells were transfected with 1 μg/ml 3p-hpRNA/LyoVec™ or incubated with 30 μg/ml 2’3’-cGAMP in the presence or absence of increasing concentrations of MRT67307. After overnight incubation, activation of IRF was assessed by measuring Lucia luciferase activity in the supernatant, using QUANTI-Luc™ detection reagent. Percentages of the maximal response for the ligand with no inhibitor are shown

2x10⁵ THP1-Dual™ cells were transfected with 1 μg/ml 3p-hpRNA/LyoVec™ with or without 1 μg/ml BX795 or 3 μg/ml MRT67307. After overnight incubation, activation of IRF was assessed by measuring Lucia luciferase activity in the supernatant using QUANTI-Luc™ detection reagent. Percentages of the maximal response for the ligand with no inhibitor are shown on the left axis. The activation NF-κB was assessed by measuring SEAP activity in the supernatant using QUANTI-Blue™ Solution detection reagent. OD at 630 nm are shown on the right axis.

Specifications

CAS number: 1190378-57-4

Solubility: 15 mg/ml in H₂O

Working concentration:  1 µM to 20 μM for cell culture assays

Formula: C₂₆H₃₆N₆O₂ . x HCl

Molecular weight: 464.60 g/mol

Quality control:

• Purity: ≥95% (UHPLC)
• Inhibition of TBK1/IKKε by MRT67307 has been confirmed using cellular assays.
• Absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ hTLR2 and HEK-Blue™ hTLR4 cells.

Contents

MRT67307 (hydrochloride) is available in two quantities:

• inh-mrt: 10 mg
• inh-mrt-3: 3 x 10 mg

MRT67307 is shipped at room temperature.

Upon receipt, store at -20 °C. 

Details

Chemical structure of MRT67307: