NT-0796: A Clinical CNS-Active NLRP3 Inhibitor Prodrug with Anti-Neuroinflammatory Activity


oral brain-penetrant NLRP3 inhibitor prodrug Ph. Ib/IIa for cardiovascular risk and neuroinflammation from SAR and prodrug development of known NLRP3 inhibitor CP-456,773 J. Med. Chem., October 2023 Nodthera, Essex, UK


NT-0796 is an ester pro-drug inhibitor of the NLRP3 inflammasome, a multi-protein complex linked to chronic inflammation, and is being developed by NodThera. NT-0796 is currently in a Ph. Ib/IIa trial in obese individuals at risk of developing atherosclerotic cardiovascular diseases. Preliminary findings from another trial in Parkinson’s disease suggest that NT-0796 has the potential to reduce neuroinflammation in the brain. The NLRP3 inflammasome has emerged as a hot target in the drug discovery arena due to its connection to various diseases, including Alzheimer’s disease, Parkinson’s disease, gout, type II diabetes, and atherosclerosis. Here is a detailed review of the role of NLRP3 inhibition in treating atherosclerosis, the competitive landscape within this therapeutic area, how NT-0796 was identified and what makes it special, recent clinical developments, and more.



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