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