PCSK9
Synonyms
FHCL3, EC 3.4.21, EC 3.4.21.111, Neural apoptosis-regulated convertase 1, Proprotein convertase 9, NARC1, PSEC0052, PCSK9, NARC-1, EC:3.4.21.-, Proprotein Convertase Subtilisin/Kexin Type 9, Subtilisin/Kexin-Like Protease PC9, PC9, Convertase Subtilisin/Kexin Type 9 Preproprotein, Hypercholesterolemia, Autosomal Dominant 3, EC 3.4.21.-, HCHOLA3, LDLCQ1, FH3, Neural Apoptosis Regulated Convertase 1,Description
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It plays a crucial role in regulating plasma cholesterol homeostasis. It binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. It acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway and may prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. It can induce ubiquitination of LDLR leading to its subsequent degradation and inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. It is involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. It inhibits epithelial Na+ channel (ENaC)-mediated Na+ absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation and regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways.
KO Status
F0
Drug Information
Launched drugs: 16
Drugs in clinical trials: 2
Latest Research Phase:Approved
Drug Name
Code
Phase
Company
Indications
Clinical Trials
HLX-16
HLX-16
Preclinical
Shanghai Fuhong Henlius Biopharmaceutical Co Ltd
Atherosclerosis, Hypercholesterolemia
Inclisiran
PCSK9si, ALN-PCSsc, KJX839, KJX-839, ALN-60212
Approved
Alnylam Pharmaceuticals Inc
Plaque, Atherosclerotic, Atherosclerosis, Diabetes Mellitus, Type 2, Kidney Diseases, Hypercholesterolemia, Dyslipidemias, Hyperlipoproteinemia Type II, Diabetes Mellitus
Evolocumab
AMG-145
Approved
Amgen Inc, Astellas Pharma Inc
Diabetes Mellitus, Type 2, Atherosclerosis, Myocardial Infarction, Hypercholesterolemia, Coronary Artery Disease, Stroke, Dyslipidemias, Coronary Disease, Cardiovascular Diseases, Hyperlipidemias, Hyperlipoproteinemia Type II, Diabetes Mellitus
Alirocumab
SAR-236553, 316P, REGN-727
Approved
Sanofi, Regeneron Pharmaceuticals Inc
Atherosclerosis, Hypercholesterolemia, Acute Coronary Syndrome, Dyslipidemias, Hyperlipoproteinemia Type II
IBI-306
IBI-306
Phase 3 Clinical
Innovent Biologics (Suzhou) Co Ltd
Hypercholesterolemia, Hyperlipoproteinemia Type II
LIB-003
LIB-003
Phase 3 Clinical
Lib Therapeutics
Hypercholesterolemia
JS-002
JS-002
Phase 3 Clinical
Shanghai Junshi Biosciences Co Ltd
Hypertriglyceridemia, Atherosclerosis, Hypercholesterolemia, Hyperlipidemia, Familial Combined, Hyperlipidemias
CiVi-007
CiVi-007, LNA-PCSK -9, LNA-PCSK9-GalNac
Phase 2 Clinical
F. Hoffmann-La Roche Ltd
Hypercholesterolemia
AK-102
AK-102
Phase 2 Clinical
Zhongshan Akeso Biopharma Co Ltd, Yabao Us Pharmaceutical Co Ltd
Hypercholesterolemia, Hyperlipidemias, Hyperlipoproteinemia Type II
SHR-1209
SHR-1209
Phase 2 Clinical
Jiangsu Hengrui Medicine Co Ltd
Hypercholesterolemia, Hyperlipidemias, Hyperlipoproteinemia Type II
Frovocimab
LY-3015014
Phase 2 Clinical
Eli Lilly And Company
Hypercholesterolemia, Hyperlipidemias
CVI-LM001
C-8304, CVI-LM001
Phase 2 Clinical
Xiwei'Ai Medicine Technology (Shanghai) Co Ltd
Hypercholesterolemia, Hyperlipidemias
Anti-PCSK9 monoclonal antibody (Biocad)
Phase 1 Clinical
Biocad
Cardiovascular Diseases
DC-371739
DC-371739
Phase 1 Clinical
Shanghai Institute Of Materia Medica, Chinese Academy Of Sciences
Hypercholesterolemia, Dyslipidemias, Hyperlipidemias
PCSK9 modulator (Genekey Biotech)
Phase 1 Clinical
Shenzhen Salubris Pharmaceuticals Co Ltd
Metabolic Diseases, Inflammation
Recombinant human anti-PCSK9 monoclonal antibody (Salubris)
SAL003
Phase 1 Clinical
Shenzhen Salubris Pharmaceuticals Co Ltd
Hypercholesterolemia, Dyslipidemias
ATH-04
ATH-04
Phase 1 Clinical
Affiris
Atherosclerosis
Recombinant human anti-PCSK9 monoclonal antibody (Tasly Pharm)
Phase 1 Clinical
Tasly Pharmaceutical Group Co Ltd
Hypercholesterolemia
SAL-092
SAL092, SAL-092
Phase 1 Clinical
Shenzhen Salubris Pharmaceuticals Co Ltd
Hypercholesterolemia, Dyslipidemias
BMS-962476
BMS-962476
Pending
Bristol-Myers Squibb Company
Atherosclerosis, Hypercholesterolemia