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High Throughput Screening Assays for NOD1 Inhibitors - Probe 1.

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Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-.
2010 Jan 23 [updated 2010 Oct 20].

Excerpt

The modulation of immune response activity is one of the major goals in the development of novel therapeutics for human immune or inflammatory diseases. The innate system resides at the intersection of the pathways of microbial recognition, inflammation, and cell death, thereby offering various therapeutic targets. In this context, NOD1 and NOD2 are of particular interest, since they recognize distinct structures derived from bacterial peptidoglycans and directly activate the NF-κB pathway, which controls the production of proinflammatory molecules. Mutations in the NOD1 and NOD2 genes are associated with a number of human inflammatory disorders, including Crohn's disease (CD), Blau syndrome, early-onset sarcoidosis, and atopic diseases, which characteristically cause constitutive NF-κB activation. Thus, small molecule inhibitors of NOD1 would provide powerful research tools for elucidating the roles of these proteins in immune response in primary cultured cells from humans and in animal models. The probe molecule ML130 (CID-1088438) selectively inhibits NOD1-dependent activation of NF-κB pathways, with selectivity over other pathways.

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