INTRODUCTION: Proprotein convertase subtilisin/kexin 9 (PCSK9) modulates the circulating levels of low-density lipoprotein cholesterol (LDL-C). Consequently, PCSK9 inhibition, at any level, from the mRNA transcription to the final interaction with LDL-R, through suitable ligands has been established as a corroborated therapeutic strategy for fighting hypercholesterolemia, preventing the risks of cardiovascular diseases. AREA COVERED: Patent literature published between 2024 and 2025 in the Espacenet database, an international repository containing more than 150 million documents from over 100 patent‑granting authorities, focusing on disclosures claiming novel compounds designed to bind and inhibit the PCSK9 protein. EXPERT OPINION: The clinical development of small-molecule PCSK9 inhibitors, such as MK-0616 (enlicitide) and AZD0780 (laroprovstat), demonstrates that PCSK9 is still a drug target of great interest for both academic and pharmaceutical companies. The numerous patents deposited in the last two years cover compounds that are structurally related to previously deposited general structures as well as newly developed scaffolds that include quinolines and isoquinolines, peptides, pyridine, and benzothiazole derivatives. However, with mAbs and siRNAs dominating the market, small molecules are required to prove superior cost-efficiency, combination value, and cardiovascular advantages that extend beyond LDL-C reduction.
Fassi et al. (Thu,) studied this question.