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

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 [...]

On Mar. 14th, 2024, resmetirom (REZDIFFRA™) became the first and only medicine approved by the FDA for the treatment of NASH (non-alcoholic steatohepatitis, aka MASH). Resmetirom, an oral, liver-targeting, once-daily THR-β-selective agonist originally discovered at Roche Nutley, was first highlighted as a Molecule of the Month in Dec. 2022. Now, with the FDA’s accelerated approval, this 2023 Molecule of the Year nominee reflects a historic milestone for liver drug discovery. This article reviews how the molecule works, how it was discovered, and why it’s a big deal.

Merck’s macrocyclic PCSK9 protein-protein interaction (PPI) inhibitor, MK-0616, is a once-daily PCSK9-lowering and LDL-cholesterol-lowering small molecule that has recently demonstrated antibody-like efficacy as an oral agent in the clinic. The program highlights numerous technical achievements at the forefront of modern drug discovery, and will set a standard for modern “classics in drug discovery” for some time.