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NI-0101 is a humanized mAb that binds specifically and selectively to human Toll-like receptor 4 (TLR4). Although the Toll-like receptor family has evolved to initiate responses to microbial insults, dysregulation is associated with the continued perpetuation of processes underlying both acute (e.g. sepsis, intensive care induced lung injury) and chronic (e.g. arthritis) inflammation. The sustained TLR4 signaling may be through prolonged exposure to external ligands (e.g. bacterial or viral products), inflammation-induced de novo generation of internal ligands (e.g. apoptotic cell proteins) and/or proteins that amplify TLR4 signaling (e.g. house dust mite antigen, Der p 2) suggesting that its unbalanced signaling is responsible for the pathologic effect. NI-0101 binds to an epitope on TLR4 which interfers with its dimerization required for intracellular signalling and induction of numerous pro-inflammatory pathways. Thus, NI-0101 will block at the level of signal transduction for any ligand source.
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