Related Experiment Video
Updated: May 19, 2026
08:14
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Proprotein convertase subtilisin/kexin type 9 inhibition
David A Marais1, Dirk J Blom, Francine Petrides
1Department of Chemical Pathology bDepartment of Medicine, University of Cape Town, Cape Town, South Africa.
Current Opinion in Lipidology
|August 22, 2012
Summary
Inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) safely lowers LDL cholesterol with statins. Monoclonal antibodies targeting PCSK9 show promising clinical trial results for cardiovascular disease management.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Pharmacology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently identified protein crucial for regulating LDL cholesterol levels.
- PCSK9 inhibition offers a novel therapeutic strategy for managing hypercholesterolemia.
Purpose of the Study:
- To review the discovery, structure, and function of PCSK9.
- To summarize the therapeutic potential of PCSK9 inhibition, particularly in conjunction with statins.
- To highlight advancements in strategies for PCSK9 inhibition and their clinical trial outcomes.
Main Methods:
- Literature review of studies on PCSK9 discovery and function.
- Analysis of clinical trial data for PCSK9 inhibitors.
- Summary of ongoing therapeutic development strategies for PCSK9 inhibition.
Main Results:
- PCSK9 inhibition demonstrates synergistic LDL cholesterol-lowering effects with statins.
- Monoclonal antibodies targeting PCSK9 are in advanced clinical trials (Phase III).
- Early-phase clinical trials (Phase I and II) show promising results for PCSK9 inhibition strategies.
Conclusions:
- PCSK9 inhibition is a safe and effective strategy for reducing LDL cholesterol.
- Monoclonal antibodies represent the most advanced therapeutic approach for PCSK9 inhibition currently.
- Further research and clinical development are ongoing for PCSK9-targeted therapies.
Related Concept Videos
01:30Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
00:46Feedback Inhibition
Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...