BAY 1217224 (Bayer oral non-prodrug thrombin (Factor IIa) inhibitor)

NT-0796 is NodThera's pro-drug inhibitor of the NLRP3 inflammasome. NT-0796 is currently in a Ph. Ib/IIa trial in obese individuals at risk of developing atherosclerotic cardiovascular diseases. NT-0796 has the potential to reduce neuroinflammation in Parkinson’s disease. The NLRP3 inflammasome has emerged as a hot target due to its connection to Alzheimer’s disease, Parkinson’s disease, gout, and other diseases. Here is a detailed review of the role of NLRP3 inhibition in treating atherosclerosis, how NT-0796 was identified, and what makes it special, clinical development, and more.

BI-0115 inhibits the C-type lectin family member lectin-like oxidized LDL-receptor-1 (LOX-1) by stabilizing an inactive tetrameric form of the protein. Interestingly, co-crystollography demonstrates that inter-ligand interactions between two BI-0115 molecules contribute to the dimerization of LOX-1 homodimers.

Novartis' NLRP3 inhibitor, NVP-DFV890, features a unique sulfonimidamide motif designed to reduce hydrolysis relative to traditional sulfonylureas. This potent compound, with promising PK in humans, is advancing through multiple clinical studies, including Ph. II trials for coronary heart disease and knee osteoarthritis. Presented by Angela Mackay at the EFMC-ISMC 2024 joint conference in Rome, this overview covers NVP-DFV890's discovery, as well as its preclinical PK and PD data.

The Merck CETP inhibitor backup, MK-8262 , is potential best-in-class CETP inhibitor, which was only discontinued as a backup due to the success of its predecessor, anacetrapib in Ph. III. Reviewer Kim Huard thought this CETP inhibitor was a great piece of work from Merck, and is a great example how to deal with a very lipophilic binding site [...]