Novel Inhibitors of Toll Like Receptor 4 for the Prevention and Treatment of Inflammatory Disorders

Unmet Need / Invention Novelty: TLR4 (Toll-like receptor 4) is the most upstream receptor in the pro-inflammatory cascade for endotoxin lipopolysaccharide (LPS). While normally downregulated gradually after full-term birth, high levels of TLR4 expression in infants born prematurely is associated with the development of NEC (necrotizing enterocolitis), a leading cause of premature infant mortality from gastrointestinal disease.

Technical Details: Researchers at Johns Hopkins University and the University of Pittsburgh have developed small molecule TLR4 inhibitors to limit inflammatory signaling as a prevention/treatment strategy against NEC.

Candidate molecules were validated in in vivo endotoxemia and NEC mouse models, respectively, and show potent activity in ameliorating the pathogenesis of NEC.

Value Proposition:

·      Novel small molecule TLR4 inhibitors to treat or prevent NEC

·      Modulation of upstream signaling may avoid the pitfalls associated with other cytokine inhibitors that act further downstream in the pathway

·      Useful to treat infectious, inflammatory, and post-traumatic disorders

Looking for Partners to: Develop & commercialize the technology as novel small molecule inhibitors of TLR4 to prevent/treat NEC and other TLR4-mediated inflammatory disorders.

Stage of Development: in vivo data  

Data Availability: In vivo endotoxemia and NEC mouse data