Dorzagliatin (Hua Medicine) is an oral dual-acting full glucokinase (GK) activator being developed for type 2 diabetes . More than 50 years since the first report of the role of GK in glucose metabolism, no agents targeting this enzyme have been approved, although not for lack of trying. We recently covered a partial GK activator [...]

“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 [...]

OATD-01 (OncoArendi Therapeutics oral, first-in-class CHIT1/AMCase chitinase inhibitor clinical candidate)

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.

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 [...]