PMID: 9187269Jun 1, 1997Paper

P-glycoprotein substrates and antagonists cluster into two distinct groups

Molecular Pharmacology
S ScalaS E Bates

Abstract

To gather further insight into the interaction between P-glycoprotein (Pgp) and its substrates, 167 compounds were analyzed in multidrug resistant human colon carcinoma cells. These compounds were selected from the National Cancer Institute Drug Screen repository using computer-generated correlations with known Pgp substrates and antagonists. The compounds were prospectively defined as Pgp substrates if cytotoxicity was increased > or =4-fold by the addition of cyclosporin A (CsA) and as Pgp antagonists if inhibition of efflux increased rhodamine accumulation by 4-fold. Among the 84 agents that met either criterion, 35 met only the criterion for substrates, 42 met only the criterion for antagonists, and only seven met both criteria. Thus, compounds interacting with Pgp form two distinct groups: one comprising cytotoxic compounds that are transported and have poor or no antagonistic activity and a second comprising compounds with antagonistic activity and no evidence of significant transport. Vinblastine accumulation and kinetic studies performed on a subset of 18 compounds similarly differentiated substrates and antagonists, but inhibition of 3H-azidopine labeling and induction of ATPase activity did not. These data support an ...Continue Reading

References

Sep 1, 1992·British Journal of Haematology·C LudescherJ Hofmann
Nov 11, 1991·International Journal of Cancer. Journal International Du Cancer·G M LaiS E Bates
Jul 4, 1990·Journal of the National Cancer Institute·P SkehanM R Boyd
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A R Safa
Apr 28, 1995·The Journal of Biological Chemistry·F J SharomK J Ashbourne
Jan 1, 1993·Cytotechnology·J M Ford, W N Hait
Jan 1, 1993·Annual Review of Biochemistry·M M Gottesman, I Pastan

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Citations

Jun 19, 2004·Journal of Drug Targeting·Remigijus DidziapetrisAlanas Petrauskas
Jul 22, 2008·Journal of Veterinary Pharmacology and Therapeutics·M MartinezK Mealey
Jun 7, 2013·Interdisciplinary Sciences, Computational Life Sciences·Rajnish KumarRajesh Kumar Tiwari
Aug 25, 2016·Nucleosides, Nucleotides & Nucleic Acids·Galal ElgemeieMai Hamed
Jan 4, 2017·Nucleosides, Nucleotides & Nucleic Acids·Galal ElgemeieAyman Farag
Apr 1, 2017·Nucleosides, Nucleotides & Nucleic Acids·Galal H Elgemeie, Ayman B Farag
Feb 2, 2018·Nucleosides, Nucleotides & Nucleic Acids·Galal H ElgemeieGalal A Nawwar
Sep 29, 2018·Scientific Reports·Iva GuberovićMarijeta Kralj
Jun 3, 1999·European Journal of Clinical Investigation·J Robert
Jan 23, 2003·Nucleosides, Nucleotides & Nucleic Acids·Galal H Elgemeie, Mona A Ahmed
Oct 10, 2003·Nucleosides, Nucleotides & Nucleic Acids·Adel M E Attia, Ashraf A El-Shehawy
Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Atsushi WadaKatsuhiko Okumura
Mar 8, 2003·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·M Barecki-RoachW W Johnson
Aug 18, 2004·Fundamental & Clinical Pharmacology·M MolimardM Strolin Benedetti
Jun 25, 2009·Assay and Drug Development Technologies·Kyle R BrimacombeKing-Leung Fung
Jan 27, 2012·Macromolecular Bioscience·Kirk D Fowers, Jindřich Kopeček
Jul 15, 2015·Nucleosides, Nucleotides & Nucleic Acids·G H Elgemeie, N M Saber
Aug 19, 2014·Nature Reviews. Drug Discovery·Katrina J Falkenberg, Ricky W Johnstone
May 4, 2018·Nucleosides, Nucleotides & Nucleic Acids·Galal H Elgemeie, Dina H El-Naggar
Feb 8, 2019·Nucleosides, Nucleotides & Nucleic Acids·Galal H ElgemeieReham A Mohamed
Dec 25, 2019·Acta Crystallographica. Section E, Crystallographic Communications·Mamdouh A Abu-ZaiedPeter G Jones
Jul 1, 2020·Nucleosides, Nucleotides & Nucleic Acids·Galal H ElgemeieAisha M Bin Yahab
Jan 7, 2005·The Journal of Pharmacology and Experimental Therapeutics·Jim J XiaoKenneth K Chan
Apr 19, 2002·Molecular Pharmacology·Sean EkinsSteven A Wrighton
Aug 25, 2016·Nucleosides, Nucleotides & Nucleic Acids·Mohammed E AzabAbd El-Galil E Amr

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