NOD2 Signaling Inhibitor II, GSK717

A cell-permeable benzimidazole diamide compound that acts as a potent, selective, reversible and muramyl dipeptide (MDP)-induced NOD2 (MDP/nucleotide-binding oligomerization domain 2)-mediated signaling inhibitor (IC₅₀ = 400 nM for MDP-stimulated IL-8 secretion in HEK293/hNOD2 cells). Does not affect NOD1, TNFR1, or TLR-2-mediated responses. Also shown to diminish synergy between NOD2 and TLR2. Reduces MDP-stimulated IL-8, IL-6, IL-1β, and TNFα release in primary human monocytes (~5 µM), but does not affect Pam₂CSK₄-stimulated IL-8 release. Due to a lack of typical activation loop/hinge-binding motif it is unlikely to act as a kinase inhibitor. NOD1 Inhibitor, Nodinitib-1 (>Cat. No. 488004) is also available.

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.

A cell-permeable benzimidazole diamide compound that selectively inhibits muramyl dipeptide/MDP-induced, nucleotide-binding oligomerization domain 2/NOD2-mediated cytokine production (% inhibiton/cytokine = 91%/IL-8, 89%/IL-6, 87%/IL-1β, 80%/TNFα 25 h post 5 µM drug addition & 24 h post 100 ng/mL MDP stimulation) in primary human monocyte cultures, but not but not TLR2/6 agonist Pam₂CSK₄- (100 pg/mL) stimulated IL-8 secretion even at concentrations as high as 16 µM. Based on selectivity studies using the less potent, non-N-methylated analog GSK669, GSK717 is not expected to act as a kinase inhibitor or display significant potency against MDP-independent NOD2 activation, TNFα receptor- and NOD1-mediated cytokine productions. A great complement to the NOD1 signaling-selective inhibitor Nodinitib-1 (Cat. No. Cat. No. 488004). The exact mechanism of inhibition is not yet determined.

Cell permeable: yes

Primary Target
NOD2

Reversible: yes

Target IC₅₀: 400 nM for MDP-stimulated IL-8 secretion in HEK293/hNOD2 cells

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Rickard, D.J., et al. 2013. PLoS ONE.D408, e69619.

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