AstraZeneca recently disclosed the structure and discovery journey of their oral small molecule PCSK9 inhibitor, AZD0780, during the ACS Fall 2024 First Time Disclosures session in Denver. Discover how the team identified a fragment hit targeting a previously unexplored pocket, verified its novel mechanism of action, and successfully advanced it into a clinical compound now in Ph. II trials for patients with dyslipidemia.

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 [...]

BMS-986235/LAR-1219 is an FPR1-sparing FPR2-selective agonist intended to help resolve chronic inflammation/promote wound healing to prevent serious complications like heart failure. It’s a very efficient molecule and is orally efficacious in a mouse myocardial infarction model at doses as low as 0.3 mg/pk, despite having 3 N-H donors (urea + [...]

Compound 20 is a galactose-based monosaccharide Gal-3 inhibitor from Bristol Myers Squibb that shows potential in targeting fibrotic diseases.

asundexian (BAY2433334) is a reversible Factor XIa active site inhibitor previously disclosed at the 2021 EFMC-ISMC conference . This article highlights the Ph. I data of asundexian in healthy volunteers, showing that the drug is well tolerated, with no clinically relevant bleeding-related adverse events or any relevant CYP3A4 modulation. The [...]