NX-13 (Amelenodor) is an orally active, gut-restricted NLRX1 agonist, has in situ binding effects on the stability of NLRX1 with EC50 of 58 nM.
NX-13 modulates CD4+ T cell differentiation and metabolism, NX-13 significantly decreased the differentiation of Th1 and Th17 at 0.05 μM with a dose response and suppressive effect down to 0.005 μM.
NX-13 (10 mg/kg, oral) reduces inflammation in a model of DSS colitis.
NX-13 reduces inflammation and alters NLRX1 signaling in PBMCs from ulcerative colitis (UC) patients, decreases NF-κB activity, TNFα+ and IFNγ+ CD4+ T cells and overall production of IL-6, MCP1 and IL-8.
NX-13 is a promising immunometabolic oral, gut-restricted therapeutic for CD and UC that is effective at reducing inflammation in DSS, adoptive transfer and Mdr1a−/− mouse models of IBD plus in in vitro studies using primary murine and human cells.
NLRX1 (Nucleotide-binding oligomerization domain, leucine rich repeat containing X1) is a mitochondria-associated receptor involved in down-regulating inflammation during bacterial and viral exposure, acute non-infectious colitis, colorectal cancer and chronic pulmonary disease.