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Related Concept Videos

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 Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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...
ABC Transporters: Exporter01:31

ABC Transporters: Exporter

ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
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,...

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Related Experiment Video

Updated: May 22, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy.

J A Sprowl1, V Gregorc, C Lazzari

  • 1Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA.

Clinical Pharmacology and Therapeutics
|April 27, 2012
PubMed
Summary

ABCC2 transporter does not significantly impact cisplatin resistance or efficacy in cancer patients. In vitro findings on drug-transporter interactions require verification in human studies.

Related Experiment Videos

Last Updated: May 22, 2026

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
09:19

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo

Published on: February 6, 2015

Area of Science:

  • Pharmacogenomics
  • Cancer Biology
  • Drug Metabolism

Background:

  • The ATP-binding cassette subfamily 2 (ABCC2), also known as multidrug resistance-associated protein 2 (MRP2) or canalicular multispecific organic anion transporter (cMOAT), is a transporter protein.
  • In vitro studies suggest a role for ABCC2 in conferring resistance to platinum-based chemotherapy agents like cisplatin.
  • Understanding the in vivo relevance of ABCC2 in cisplatin response is crucial for optimizing cancer therapy.

Purpose of the Study:

  • To investigate the association between ABCC2 genetic variations and cisplatin pharmacokinetics and efficacy in cancer patients.
  • To evaluate the impact of Abcc2 knockout on cisplatin disposition and toxicity in a murine model.
  • To determine if ABCC2 single-nucleotide polymorphisms (SNPs) correlate with ABCC2 expression and cisplatin-induced cytotoxicity.

Main Methods:

  • Analysis of cisplatin pharmacokinetics and efficacy in 237 cancer patients, correlating with seven common ABCC2 SNPs.
  • Assessment of cisplatin disposition and toxicity in Abcc2 knockout (Abcc2−/−) mice.
  • Correlation analysis of ABCC2 SNPs with ABCC2 expression in the NCI60 cell line panel and with cisplatin-induced cytotoxicity.

Main Results:

  • Abcc2 knockout did not alter cisplatin disposition or toxicity in mice.
  • No significant association was found between the studied ABCC2 SNPs and cisplatin pharmacokinetics (P > 0.12) or efficacy (P > 0.41) in cancer patients.
  • The investigated ABCC2 SNPs did not correlate with ABCC2 expression in the NCI60 panel (P > 0.26) or with cisplatin-induced cytotoxicity (P = 0.21).

Conclusions:

  • ABCC2 genetic variations do not appear to be significant determinants of cisplatin pharmacokinetics or clinical efficacy in the studied patient cohort.
  • In vivo and human clinical data suggest that the role of ABCC2 in cisplatin resistance observed in vitro may not translate to clinical relevance.
  • These findings underscore the necessity of validating in vitro drug-transporter interactions through human studies to accurately predict clinical outcomes.