title: Tandutinib (MLN518/CT53518) targeted to stem-like cells by inhibiting the function of ATP-binding cassette subfamily G member 2.
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 [H(3)] 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou 510060, China.
authors.forename: Xiao-qin
authors.initials: XQ
authors.lastname: Zhao
authors.forename: Chun-ling
authors.initials: CL
authors.lastname: Dai
authors.forename: Shinobu
authors.initials: S
authors.lastname: Ohnuma
authors.forename: Yong-ju
authors.initials: YJ
authors.lastname: Liang
authors.forename: Wen
authors.initials: W
authors.lastname: Deng
authors.forename: Jun-Jiang
authors.initials: JJ
authors.lastname: Chen
authors.forename: Mu-Sheng
authors.initials: MS
authors.lastname: Zeng
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Ambudkar
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Chen
authors.forename: Li-Wu
authors.initials: LW
authors.lastname: Fu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008942:Mitoxantrone / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000494:pharmacology*; D020112:Rhodamine 123 / Q000494:pharmacology
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D020112:Rhodamine 123; D004317:Doxorubicin; D008942:Mitoxantrone; C464670:tandutinib; D011505:Protein-Tyrosine Kinases; D000251:Adenosine Triphosphatases