Identification of compounds selectively killing multidrug-resistant cancer cells

Dóra Türk, Matthew D. Hall, Benjamin F. Chu, Joseph A. Ludwig, Henry M. Fales, Michael M. Gottesman, G. Szakács

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

There is a great need for the development of novel chemotherapeutic agents that overcome the emergence of multidrug resistance (MDR) in cancer. We catalogued the National Cancer Institute's DTPdrug repository in search of compounds showing increased toxicity in MDR cells. By comparing the sensitivity of parental cell lines with MDR derivatives, we identified 22 compounds possessing MDR-selective activity. Analysis of structural congeners led to the identification of 15 additional drugs showing increased toxicity in Pgp-expressing cells. Analysis of MDR-selective compounds led to the formulation of structure activity relationships and pharmacophore models. This data mining coupled with experimental data points to a possible mechanism of action linked to metal chelation. Taken together, the discovery of the MDR-selective compound set shows the robustness of the developing field of MDR-targeting therapy as a new strategy for resolving Pgp-mediated MDR.

Original languageEnglish
Pages (from-to)8293-8301
Number of pages9
JournalCancer Research
Volume69
Issue number21
DOIs
Publication statusPublished - Nov 1 2009

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Multiple Drug Resistance
Neoplasms
Data Mining
National Cancer Institute (U.S.)
Structure-Activity Relationship
Metals
Cell Line
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Türk, D., Hall, M. D., Chu, B. F., Ludwig, J. A., Fales, H. M., Gottesman, M. M., & Szakács, G. (2009). Identification of compounds selectively killing multidrug-resistant cancer cells. Cancer Research, 69(21), 8293-8301. https://doi.org/10.1158/0008-5472.CAN-09-2422

Identification of compounds selectively killing multidrug-resistant cancer cells. / Türk, Dóra; Hall, Matthew D.; Chu, Benjamin F.; Ludwig, Joseph A.; Fales, Henry M.; Gottesman, Michael M.; Szakács, G.

In: Cancer Research, Vol. 69, No. 21, 01.11.2009, p. 8293-8301.

Research output: Contribution to journalArticle

Türk, D, Hall, MD, Chu, BF, Ludwig, JA, Fales, HM, Gottesman, MM & Szakács, G 2009, 'Identification of compounds selectively killing multidrug-resistant cancer cells', Cancer Research, vol. 69, no. 21, pp. 8293-8301. https://doi.org/10.1158/0008-5472.CAN-09-2422
Türk D, Hall MD, Chu BF, Ludwig JA, Fales HM, Gottesman MM et al. Identification of compounds selectively killing multidrug-resistant cancer cells. Cancer Research. 2009 Nov 1;69(21):8293-8301. https://doi.org/10.1158/0008-5472.CAN-09-2422
Türk, Dóra ; Hall, Matthew D. ; Chu, Benjamin F. ; Ludwig, Joseph A. ; Fales, Henry M. ; Gottesman, Michael M. ; Szakács, G. / Identification of compounds selectively killing multidrug-resistant cancer cells. In: Cancer Research. 2009 ; Vol. 69, No. 21. pp. 8293-8301.
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