A review of PCSK9 inhibition and its effects beyond LDL receptors.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an integral role in the degradation of low-density lipoprotein receptors (LDL-R), making it an intriguing target for emerging pharmacotherapy. Two PCSK9 inhibitors, alirocumab and evolocumab, have been approved and are available in the United States and European Union. However, much of the PCSK9 story remains to be told. The pipeline for additional pharmacotherapy options is rich with several compounds under development, using alternative strategies for inhibiting PCSK9. Perhaps, more intriguing is the interaction between PCSK9 and non-LDL-R targets, including mediators of inflammation and immunological processes, which remain under intense investigation. This review will discuss the currently available PCSK9 inhibitors, the development of novel approaches to PCSK9 modulation, and the potential non-LDL-R-mediated effects of PCSK9 inhibition.
Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA. Electronic address: dldixon@vcu.edu.
Dave L
DL
Dixon
Department of Cardiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Cory
C
Trankle
Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
Leo
L
Buckley
Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
Eric
E
Parod
Department of Cardiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Salvatore
S
Carbone
Department of Pharmacotherapy & Outcomes Science, Virginia Commonwealth University School of Pharmacy, Richmond, VA, USA.
Benjamin W
BW
Van Tassell
Department of Cardiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Antonio
A
Abbate
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018955:CD36 Antigens / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018955:CD36 Antigens; D000091362:PCSK9 Inhibitors; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D054852:Small Molecule Libraries; D000071449:Proprotein Convertase 9; C571059:alirocumab
Alirocumab; Dyslipidemia; Evolocumab; PCSK9