13PCSK9i

13PCSK9i is a macrocyclic small-molecule inhibitor designed to disrupt the interaction between Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) and the Low-Density Lipoprotein Receptor (LDLR). Identified through an affinity-based screen of macrocyclic peptides by the Novartis Institutes for BioMedical Research and PeptiDream, it utilizes a novel, induced-fit allosteric pocket on PCSK9. With a molecular weight of approximately 1.65 kDa, it is recognized as the smallest molecule to date demonstrating in vivo PCSK9-LDLR disruptor function. In preclinical mouse models, subcutaneous administration of 13PCSK9i significantly increased hepatic LDLR density and reduced plasma total cholesterol levels by up to 43%, performing comparably to PCSK9 monoclonal antibodies. It is being investigated for the treatment of hypercholesterolemia and the reduction of cardiovascular disease risk.