3区 · 医学
Article
作者: Pettersen, Daniel ; Hurt-Camejo, Eva ; Nordberg, Peter ; Castaldo, Marie ; Giordanetto, Fabrizio ; Knerr, Laurent ; Larsson, Lars-Olof ; Sandmark, Jenny ; Karlsson, Ulla ; Starke, Ingemar ; Dekker, Niek ; Rosengren, Birgitta ; Selmi, Nidhal ; Dahlström, Mikael
Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A2 (sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease.