NLRX1 is a highly conserved nucleotide-binding domain (NBD) and a member of the leucine-rich repeat (LRR) family (NLR). Specifically, NLRX1 is an intracellular protein that plays a role in the immune system. Besides, NLRX1 affects innate immunity to the virus by interfering with the mitochondrial antiviral signal protein (MAVs)/retinoic acid-induced gene I (RIG-I) mitochondrial antiviral pathway. Consistent with the conserved motif structure of the NLR family, NLRX1 contains a central putative NBD and carboxyl-terminal LRR. Moreover, NLRX1 showed negative regulation of type I interferon and decreased pro-inflammatory NF- κB signal transduction. NLRX1 promotes the production of reactive oxygen species and regulates autophagy, cell death, and proliferation. Furthermore, NLRX1 significantly affects a variety of diseases, including cancer, viral infection, osteoarthritis, traumatic brain injury and inflammatory bowel disease. NLRX1 is widely expressed in mammalian cells.
NLRX1 is unique in the NLR family. Because of its intracellular localization on mitochondria and its ability to negatively regulate type I interferon signal transduction and inflammatory cytokine response. NLRX1 acts as an in vivo checkpoint for IFN-I and IL-6 responses in NLRX1, TRAF6 and NF- κ B establish a link between signal transduction. NLRX1 is important in response to ROS induction by pathogens. Here, we will introduce a selective, orally active NLRX1 activator, NX-13.
NX-13 Targets and Activates NLRX1 to Induce Immunometabolic Changes.
Firstly, NX-13 is an orally active, gut-restricted novel drug candidate. Meanwhile, NX-13 targets and activates NLRX1 to induce immunometabolic changes resulting in lower inflammation and responses in inflammatory bowel disease. Nonetheless, NX-13 is a promising drug for Crohn’s disease and ulcerative colitis research.
Secondly, NX-13 decreases differentiation into Th1 and Th17 subsets in naive CD4+ T cells. Importantly, NX-13 increased oxidative phosphorylation and decreased NF-κB activation and reactive oxygen species. Particularly, NX-13 with 500-1000 mg/kg by oral gavage for 7 days reduces ALP levels. Obviously, NX-13 has a higher elimination rate constant and lower half-life.
Finally, NX-13 is a selective, orally active, gut-restricted NLRX1 activator.