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.

“Compound 10” (AstraZeneca) is an oral CDK5-mediated PPARγ phosphorylation inhibitor and partial PPARγ agonist being developed as an antidiabetic drug . Although widely used PPARγ agonists such as rosiglitazone and pioglitazone are effective antidiabetics, they are limited by [...]

Peptidic GLP-1R agonists have received significant media coverage over the past year. Shortages of the semaglutide-based injectable diabetes medication Ozempic, which accounts for 40% of GLP-1R agonist US market share, have even emerged, driven by overwhelming demand for the weight loss formulation Wegovy, both for treatment of obesity and for short-term weight loss popularized by celebrities on social media. This article reviews the science of danuglipron, recent news, and what makes it different.

dotinurad (FYU-981) potently inhibits uric acid uptake by renal proximal tubule epithelial cells, increasing uric acid urinary secretion which can help hyperuricemic conditions like gout. The mechanism of action is believed to be inhibition of the URAT1 organic anion transporter which mediates uric acid reabsorption. Benzbromarone has been [...]

PF-06835919 is an oral first-in-class clinical candidate for NAFLD/NASH targeting ketohexokinase (KHK), an enzyme which initiates the metabolism of fructose. The authors describe a very elegant structure-based design campaign to improve a modestly active, quickly cleared lead molecule into this highly potent, permeable, bioavailable, and [...]