In vitro and in vivo evaluation of WK-X-34, a novel inhibitor of P-glycoprotein and BCRP, using radio imaging techniques

International Journal of Cancer. Journal International Du Cancer
Veronika JekerleMichael Wiese

Abstract

Overexpression of the multidrug resistance proteins P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) results in treatment failure of many malignancies including ovarian cancer. Dual inhibition of Pgp and BCRP may restore the sensitivity of resistant cells to anticancer drugs. We report the synthesis and characterization of a novel anthranilic-acid based Pgp and BCRP modulator, WK-X-34. In vitro inhibition of Pgp activity was evaluated using 99mTc-Sestamibi and daunorubicin accumulation in Pgp overexpressing human ovarian cancer cells (A2780/Adr) and its sensitive counterpart (A2780/wt). Interaction with BCRP was examined with a mitoxantrone-efflux assay in BCRP-overexpressing MCF7/mx cells, with flow cytometry. Interactions with the multidrug resistance associated proteins (MRP) were evaluated in transfected MRP1, MRP2 and MRP3 cell lines, using a 5-CFDA efflux assay. In vivo 99mTc-Sestamibi imaging of human ovarian cancer xenografts was used to evaluate the in vivo efficacy of WK-X-34 in mice. Daunorubicin accumulation in A2780/Adr cells was inhibited by WK-X-34 at nanomolar concentrations (IC50: 82.1 +/- 6 nM). WK-X-34 inhibited mitoxantrone accumulation in BCRP-overexpressing cells at micromolar concentration...Continue Reading

References

Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Apr 1, 1989·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W S DaltonS E Salmon
Dec 29, 1995·The American Journal of Medicine·V Ling
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·P Borst, A H Schinkel
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G A FisherB I Sikic
Mar 18, 1999·European Journal of Nuclear Medicine·N H HendrikseE G de Vries
Mar 31, 1999·Proceedings of the National Academy of Sciences of the United States of America·V V RaoD Piwnica-Worms
Nov 24, 1999·The Journal of Clinical Investigation·J W SmitA H Schinkel
Aug 17, 2000·Journal of the National Cancer Institute·P BorstJ Wijnholds
Sep 7, 2000·Current Opinion in Oncology·B TanL Ratner
Oct 18, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·R Krishna, L D Mayer
Jun 16, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R A PeckM J Hawkins
Aug 31, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H GelderblomA Sparreboom
Nov 8, 2001·Canadian Journal of Physiology and Pharmacology·G Lee, M Piquette-Miller
Jun 5, 2002·Annual Review of Biochemistry·P Borst, R Oude Elferink
Sep 28, 2002·Journal of Magnetic Resonance Imaging : JMRI·Vijay SharmaDavid Piwnica-Worms
Nov 15, 2002·Cancer Biology & Therapy·Wafik S El-Deiry
Jun 28, 2003·European Journal of Nuclear Medicine and Molecular Imaging·Teréz MáriánZoltán Krasznai
Apr 24, 2004·European Journal of Nuclear Medicine and Molecular Imaging·Silvana Del Vecchio, Marco Salvatore
Apr 30, 2004·Journal of Medicinal Chemistry·Ilza K PajevaMichael Wiese
May 29, 2004·FEBS Letters·Balázs SarkadiAndrás Váradi
Mar 25, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Marc H G P RaaijmakersReinier A P Raymakers

❮ Previous
Next ❯

Citations

Feb 27, 2007·Cancer Metastasis Reviews·Robert W RobeySusan E Bates
Sep 7, 2006·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Veronika JekerleMicheline Piquette-Miller
Aug 28, 2012·Journal of Biomolecular Screening·J Jacob StrouseLarry A Sklar
Mar 24, 2010·Radiology·Mark B WilliamsStanislaw Majewski
Feb 6, 2008·Expert Opinion on Drug Metabolism & Toxicology·Suneet ShuklaSuresh V Ambudkar
Sep 30, 2010·Expert Opinion on Drug Metabolism & Toxicology·Maren PoguntkeOliver Zolk
Sep 29, 2009·Bioorganic & Medicinal Chemistry Letters·Hans-Georg HäckerMichael Gütschow
Mar 5, 2016·Journal of Medicinal Chemistry·Sven Marcel SchmittMichael Wiese
Mar 3, 2009·Bioorganic & Medicinal Chemistry·Werner KlinkhammerMichael Wiese
Aug 6, 2008·Bioorganic & Medicinal Chemistry·Anne PickMichael Wiese
Dec 18, 2007·Bioorganic & Medicinal Chemistry·Henrik MüllerMichael Wiese
Sep 25, 2007·Bioorganic & Medicinal Chemistry·Henrik MüllerMichael Wiese
Feb 24, 2007·Bioorganic & Medicinal Chemistry·Ahcene BoumendjelAttilio Di Pietro
Jul 22, 2015·European Journal of Medicinal Chemistry·Xu-Qin LiKenneth K W To
Jun 24, 2015·Critical Reviews in Oncology/hematology·M P WeenC Ricciardelli
Nov 27, 2014·Canadian Journal of Physiology and Pharmacology·Tianxiao ZhaoHai Qian
Jun 9, 2011·ACS Medicinal Chemistry Letters·Sonali B Fonseca, Shana O Kelley
Nov 5, 2016·Biochimica Et Biophysica Acta. Biomembranes·Sven Marcel SchmittMichael Wiese
Feb 9, 2017·Canadian Journal of Physiology and Pharmacology·Yuzhu WangLiang Ge
Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Iichiro KawaharaTakuya Fujita
Mar 9, 2011·Dalton Transactions : an International Journal of Inorganic Chemistry·Filipa MendesIsabel Santos
Sep 28, 2016·Molecular Cancer Therapeutics·Jerec W RicciRichard S Larson
Feb 9, 2021·Expert Review of Clinical Pharmacology·Yadollah OmidiHossein Omidian
Feb 6, 2020·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Jinyun DongJiang-Jiang Qin
Jan 29, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Fabian BaltesGerd Bendas
Dec 11, 2021·Bioinformatics·Vigneshwaran NamasivayamSven Marcel Stefan

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.