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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 and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
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...
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...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...

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Related Experiment Video

Updated: Jul 17, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

ABCB1 pharmacogenetics: progress, pitfalls, and promise.

L W Chinn1, D L Kroetz

  • 1Department of Biopharmaceutical Sciences and Institute for Human Genetics, University of California San Francisco, San Francisco, California, USA.

Clinical Pharmacology and Therapeutics
|January 30, 2007
PubMed
Summary

P-glycoprotein (P-gp) is a 170 kDa protein found in drug-resistant cells that affects drug permeability. Its discovery and gene identification (MDR1/ABCB1) revealed its role as an efflux transporter impacting xenobiotic response.

Related Experiment Videos

Last Updated: Jul 17, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • P-glycoprotein (P-gp) was first identified in 1976 in multidrug-resistant Chinese hamster ovary (CHO) cells.
  • Its presence correlated with altered cellular permeability to colchicine, leading to its naming.
  • Overexpression of P-gp has been observed in various tumor and leukemic cells.

Purpose of the Study:

  • To investigate the nature and function of a protein associated with drug resistance.
  • To understand the role of P-gp in cellular xenobiotic transport.
  • To identify the gene responsible for P-gp expression.

Main Methods:

  • Initial characterization of a protein in drug-resistant versus drug-sensitive cells.
  • Homology studies comparing the protein to known bacterial transporters.
  • Gene discovery and designation (MDR1/ABCB1).
  • Immunohistochemical analysis of P-gp expression in various tissues.

Main Results:

  • A 170 kDa protein (P-gp) was identified in colchicine-resistant CHO cells.
  • P-gp was found to alter cellular permeability to colchicine.
  • High homology suggested P-gp functions as an efflux transporter.
  • The gene encoding P-gp was identified as MDR1 (ABCB1).
  • P-gp expression was detected in secretory tissues and at blood-tissue barriers.

Conclusions:

  • P-glycoprotein plays a significant role in cellular drug resistance.
  • P-gp functions as an efflux transporter, modulating intracellular xenobiotic concentrations.
  • The tissue distribution of P-gp suggests its involvement in xenobiotic response and toxicity through pharmacokinetic and pharmacodynamic mechanisms.