Tandutinib (MLN518/CT53518) targeted to stem-like cells by inhibiting the function of ATP-binding cassette subfamily G member 2

Xiao Qin Zhao, Chun Ling Dai, Shinobu Ohnuma, Yong Ju Liang, Wen Deng, Jun Jiang Chen, Mu Sheng Zeng, Suresh V. Ambudkar, Zhe Sheng Chen, Li Wu Fu

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Tandutinib is a novel inhibitor of tyrosine kinases FLT3, PDGFR and KIT. Our study was to explore the capability of tandutinib to reverse ABC transporter-mediated multidrug resistance. Tandutinib reversed ABCG2-mediated drug resistance in ABCG2-482-R2, ABCG2-482-G2, ABCG2-482-T7 and S1-M1-80 cells and increased the accumulation of doxorubicin, rhodamine 123 and [H3] mitoxantrone in ABCG2-overexpressing cells. Importantly, tandutinib selectively sensitized side population cells to mitoxantrone. Taken together, our results advocate the potency of tandutinib as an ABCG2 modulator and stem-like cells targeted agent to increase efficiency of anticancer drugs.

Original languageEnglish
Pages (from-to)441-450
Number of pages10
JournalEuropean Journal of Pharmaceutical Sciences
Volume49
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • ABCG2/BCRP
  • Multidrug resistance
  • Stem-like cells
  • Tandutinib
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Pharmaceutical Science

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