Related Experiment Video

Updated: Oct 6, 2025

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
08:14

A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9

Published on: August 28, 2018

8.3K

PCSK9 as a Target for Development of a New Generation of Hypolipidemic Drugs

Nikolay Kuzmich1,2, Elena Andresyuk2, Yuri Porozov2,3

  • 1Laboratory of Drug Safety, Smorodintsev Research Institute of Influenza, WHO National Influenza Centre of Russia, 15/17 Professor Popov Street, 197376 Saint-Petersburg, Russia.

Molecules (Basel, Switzerland)
|January 21, 2022
PubMed

Insights

New cholesterol-lowering drugs targeting PCSK9 are being developed. Low-molecular-weight inhibitors offer a promising alternative to existing treatments, potentially reducing side effects and improving oral bioavailability.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) cholesterol metabolism.
  • PCSK9 inhibition increases the number of LDL receptors (LDLR) on hepatocytes, enhancing LDL clearance from the bloodstream.
  • Current lipid-lowering therapies have limitations, including side effects and high costs.

Purpose of the Study:

  • To review different classes of PCSK9 antagonists.
  • To explore various mechanisms of PCSK9 inhibition.
  • To highlight the need for novel, effective, and well-tolerated cholesterol-lowering agents.

Main Methods:

  • Literature review of existing and emerging PCSK9 inhibitors.
  • Analysis of different molecular structures and mechanisms of action.
  • Comparison of PCSK9 inhibitors with current antihyperlipidemic drugs.

Main Results:

  • PCSK9 antagonists encompass diverse compound classes, including small molecules and macromolecules.
  • Mechanisms include blocking PCSK9-LDLR binding, enhancing PCSK9 degradation, and inhibiting PCSK9 transcription or transport.
  • Existing treatments like statins and monoclonal antibodies have drawbacks; unmet needs persist.

Conclusions:

  • PCSK9 remains a significant therapeutic target for dyslipidemia.
  • Low-molecular-weight PCSK9 inhibitors represent a potential advancement in cholesterol management.
  • Further development of orally bioavailable PCSK9 inhibitors could offer improved efficacy and safety profiles.
Keywords:
LDLRPCSK9PCSK9 inhibitorsantihyperlipidemic therapylipid-lowering drugs

More Related Videos

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes10:56

A Familial Hypercholesterolemia Human Liver Chimeric Mouse Model Using Induced Pluripotent Stem Cell-derived Hepatocytes

Published on: September 15, 2018

8.3K
LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring08:45

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring

Published on: November 17, 2018

13.6K

Related Concept Videos

Lipid-Lowering Drugs: Statins and Miscellaneous Agents01:20

Lipid-Lowering Drugs: Statins and Miscellaneous Agents

Hyperlipidemia, a medical condition often referred to as high cholesterol, is characterized by abnormally elevated levels of lipids in the bloodstream. When present in excess, these lipids, specifically cholesterol and triglycerides, can lead to serious health complications, often involving cardiovascular diseases. Illnesses like atherosclerosis, heart attacks, and pancreatitis have all been linked to untreated hyperlipidemia. This means controlling and regulating cholesterol and triglyceride...
932
Atherosclerosis III: Management01:26

Atherosclerosis III: Management

Management of atherosclerosis involves an integrated strategy encompassing pharmacological treatment, surgical interventions, lifestyle changes, and nutrition therapy to address the multifactorial nature of the disease.Pharmacological TherapyA cornerstone of atherosclerosis management is the use of pharmacological agents. Statins, such as atorvastatin, are pivotal in inhibiting HMG-CoA reductase, an enzyme that catalyzes an initial step in cholesterol synthesis in the liver. This reduction in...
59
Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
7.8K
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance01:07

Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
104
Cholesterol: Significance and Regulation01:29

Cholesterol: Significance and Regulation

Although not a source of energy, cholesterol plays a significant role as a foundational structure for bile salts, steroid hormones, and vitamin D, as well as being a crucial component of plasma membranes. Approximately 15% of blood cholesterol is derived from our diet, with the remainder synthesized from acetyl CoA by the liver and intestines. Cholesterol is eliminated from the body through its conversion into bile salts, which are eventually discarded in the feces.
Considering cholesterol and...
731
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
9.3K