ML130 (Nodinitib-1)

Nodinitib-1 (ML130;CID-1088438) is a NOD1 inhibitor with an IC50 of 0.56 μM.

Nodinitib-1 selectively inhibits IL-8 production induced by NOD1 ligand. Nodinitib-1 also inhibits γ-tri-DAP-induced expression of the prototypical NF-κB target gene IκBα at the mRNA level. Nodinitib-1 inhibits γ-tri-DAP-dependent activation of NF-κB (IκBα phosphorylation and degradation) and MAPK (p38 phosphorylation) signalings, without affecting Akt survival pathway. Nodinitib-1 selectively inhibits responses of primary dendritic cells to NOD1 ligand. Nodinitib-1 reduces cell surface expression of co-stimulatory molecules CD83, CD86 and HLA-DR and also inhibits expression of IL-1β, IL-6 and TNFα elicited by γ-tri-DAP (but not by LPS), without causing cytoxicity[1]. Nodinitib-1 is identified as NOD1-selective molecules from an HTS campaign involving ~290,000 compounds. Nodinitib-1 inhibits γ-tri-DAP-stimulated luciferase production in HEK 293T cells, which has endogenous NOD1 levels at submicromolar concentration as determined in a NF-κB-linked reporter assay[2].

References:
[1]. Correa RG, et al. Discovery and characterization of 2-aminobenzimidazole derivatives as selective NOD1 inhibitors. Chem Biol. 2011 Jul 29;18(7):825-32.
[2]. Hershberger PM, et al. Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway. Beilstein J Org Chem. 2013 May 8;9:900-7.