PCSK9 Inhibition: From Current Advances to Evolving Future

Cells. 2022 Sep 23;11(19):2972. doi: 10.3390/cells11192972.


Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine protease synthesized primarily by the liver. It mainly promotes the degradation of low-density lipoprotein receptor (LDL-R) by binding LDL-R, reducing low-density lipoprotein cholesterol (LDL-C) clearance. In addition to regulating LDL-R, PCSK9 inhibitors can also bind Toll-like receptors (TLRs), scavenger receptor B (SR-B/CD36), low-density lipoprotein receptor-related protein 1 (LRP1), apolipoprotein E receptor-2 (ApoER2) and very-low-density lipoprotein receptor (VLDL-R) reducing the lipoprotein concentration and slowing thrombosis. In addition to cardiovascular diseases, PCSK9 is also used in pancreatic cancer, sepsis, and Parkinson's disease. Currently marketed PCSK9 inhibitors include alirocumab, evolocumab, and inclisiran, as well as small molecules, nucleic acid drugs, and vaccines under development. This review systematically summarized the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors, aiming to provide ideas for the drug research and development and the clinical application of PCSK9 in cardiovascular diseases and expand its application in other diseases.

Keywords: PCSK9 inhibitors; cardiovascular disease; clinical applications; research status; security.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol, LDL / metabolism
  • Humans
  • Lipoproteins, VLDL
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Nucleic Acids*
  • Proprotein Convertase 9 / metabolism
  • Subtilisins


  • Cholesterol, LDL
  • Lipoproteins, VLDL
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Nucleic Acids
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Subtilisins

Grants and funding

This work was supported by the National Natural Science Foundation of China (82104495 and 82174161), Macao Youth Scholars Program (AM2021023), Guangdong Basic and Applied Basic Research Foundation (2022A1515010395 and 2021A1515012573), Science and Technology Foundation of Guangzhou City (202102010257), State Key Laboratory of Dampness Syndrome of Chinese Medicine Research Foundation (SZ2021ZZ21), Scientific research projects of Guangdong Bureau of Traditional Chinese Medicine (No. 20212088 and 20202075), Innovative Team Project of Guangdong Province General University(2022KCXTD007), TCM Research Fund of Guangdong Provincial Hospital of Chinese Medicine (YN2020MS13), and Fund of Science and Technology Innovation Strategy of Guangdong Province (191900105), The 2022 Guangdong-Hong Kong-Macao Joint Laboratory of Traditional Chinese Medicine and Immune Diseases (MY2022KF05), The 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong-Macau Joint Lab), NO: 2020B1212030006.