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Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes01:28

Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes

Cytochrome P450 (CYP450) enzymes are a superfamily of heme-containing monooxygenases that play a pivotal role in Phase I drug metabolism by catalyzing oxidation and reduction reactions.These enzymes transform lipophilic xenobiotics into more hydrophilic metabolites, facilitating subsequent Phase II conjugation and eventual excretion. The CYP450 family is classified into families (e.g., CYP1–CYP3) and subfamilies (e.g., CYP2A, CYP2C), based on amino acid sequence homology.CYP450 isoenzymes,...
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, mediated...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...

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Related Experiment Video

Updated: Jul 3, 2026

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

PCSK9 function and physiology.

Andrew S Peterson1, Loren G Fong, Stephen G Young

  • 1Department of Molecular Biology, Genentech, South San Francisco, CA, USA. peterson.andrew@gene.com

Journal of Lipid Research
|July 30, 2008
PubMed
Summary
This summary is machine-generated.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) protein regulates LDL receptor levels, impacting plasma cholesterol. Understanding PCSK9 mutations offers new strategies for treating hypercholesterolemia and heart disease.

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LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

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

Published on: November 17, 2018

Related Experiment Videos

Last Updated: Jul 3, 2026

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

LDL Cholesterol Uptake Assay Using Live Cell Imaging Analysis with Cell Health Monitoring
08:45

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

Published on: November 17, 2018

Area of Science:

  • Lipid Metabolism
  • Molecular Biology
  • Cardiovascular Disease

Background:

  • Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma cholesterol metabolism.
  • PCSK9 influences low-density lipoprotein (LDL) receptor degradation, affecting circulating LDL cholesterol levels.
  • Genetic variations in PCSK9 are linked to hypercholesterolemia and coronary heart disease risk.

Purpose of the Study:

  • To elucidate the functional basis of hypercholesterolemia associated with PCSK9 gain-of-function mutations.
  • To investigate the kinetics and metabolism of PCSK9 and its impact on LDL receptors in hepatic and adrenal tissues.

Main Methods:

  • Functional analysis of PCSK9 gain-of-function mutations.
  • Kinetic and metabolic studies of PCSK9.
  • Assessment of PCSK9's effect on LDL receptor expression and function in vivo and in vitro.

Main Results:

  • Gain-of-function PCSK9 mutations lead to reduced hepatic LDL receptor levels, elevating plasma LDL cholesterol.
  • Loss-of-function PCSK9 mutations result in increased LDL receptor levels, lowering plasma LDL cholesterol and conferring protection against heart disease.
  • Studies detailed the molecular mechanisms underlying PCSK9's role in cholesterol homeostasis.

Conclusions:

  • PCSK9 is a critical therapeutic target for managing hypercholesterolemia.
  • Detailed understanding of PCSK9's molecular interactions and physiology is advancing treatment strategies for cardiovascular disease.
  • Further research into PCSK9 offers promise for novel hypercholesterolemia therapies.