Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

P-glycoprotein substrates and antagonists cluster into two distinct groups

S Scala1, N Akhmed, U S Rao

  • 1Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

Molecular Pharmacology
|June 1, 1997
PubMed
Summary

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Synthesis and in Vitro Anti-Tumor Activity of A New Class of Acyclic Thioglycosides.

Nucleosides, nucleotides & nucleic acids·2015
Same author

Synthesis and in vitro anti-tumor activity of new oxadiazole thioglycosides.

European journal of medicinal chemistry·2010
Same author

Sickle cell anemia; recent progress of pediatric interest.

The American journal of the medical sciences·2010
Same author

Clinical applications of bone marrow examination in childhood.

The American journal of the medical sciences·2010
Same author

Changing concepts in Mediterranean (Cooley's) anemia.

The American journal of the medical sciences·2010
Same author

GB virus C/Hepatitis G virus infection is frequent in American children and young adults.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America·2000

Compounds interacting with P-glycoprotein (Pgp) form two distinct groups: transported substrates and antagonists. This suggests Pgp utilizes multiple regions for drug transport, not specific binding sites.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Cancer Research

Background:

  • P-glycoprotein (Pgp) is a key transporter involved in multidrug resistance (MDR).
  • Understanding Pgp-substrate interactions is crucial for developing effective cancer therapies.
  • Previous studies have identified various Pgp substrates and antagonists, but their distinct interaction mechanisms remain unclear.

Purpose of the Study:

  • To investigate the distinct interaction profiles of compounds with P-glycoprotein (Pgp).
  • To differentiate between Pgp substrates and antagonists based on their functional effects.
  • To explore the structural basis of Pgp-drug interactions.

Main Methods:

  • Analysis of 167 compounds from the National Cancer Institute repository in multidrug-resistant human colon carcinoma cells.

Related Experiment Videos

  • Compounds were classified as Pgp substrates or antagonists based on cytotoxicity changes with cyclosporin A (CsA) and rhodamine accumulation.
  • Functional assays including vinblastine accumulation and kinetic studies were performed on a subset of compounds.

    • Main Results:

    • Out of 84 compounds meeting interaction criteria, 35 were identified as Pgp substrates only, and 42 as Pgp antagonists only.
    • Only seven compounds exhibited both substrate and antagonist properties.
    • Vinblastine accumulation studies corroborated the substrate/antagonist differentiation, while other assays did not consistently distinguish between the two groups.

    Conclusions:

    • Compounds interacting with Pgp can be broadly categorized into distinct groups: transported substrates and inhibitors.
    • These findings support the emerging model of Pgp function involving multiple interaction regions rather than specific binding sites.
    • This classification provides a framework for understanding Pgp modulation in cancer treatment.