Tricyclic isoxazoles are novel inhibitors of the multidrug resistance protein (MRP1).

  title={Tricyclic isoxazoles are novel inhibitors of the multidrug resistance protein (MRP1).},
  author={B. Norman and J. Gruber and S. Hollinshead and J. W. Wilson and J. Starling and K. Law and T. D. Self and L. Tabas and D. C. Williams and D. Paul and M. Wagner and A. Dantzig},
  journal={Bioorganic & medicinal chemistry letters},
  volume={12 6},
  • B. Norman, J. Gruber, +9 authors A. Dantzig
  • Published 2002
  • Chemistry, Medicine
  • Bioorganic & medicinal chemistry letters
  • Tricyclic isoxazoles were identified from a screen as a novel class of selective multidrug resistance protein (MRP1) inhibitors. From a screen lead, SAR efforts resulted in the preparation of LY 402913 (9h), which inhibits MRP1 and reverses drug resistance to MRP1 substrates, such as doxorubicin, in HeLa-T5 cells (EC(50)=0.90 microM), while showing no inherent cytotoxicity. Additionally, LY 402913 inhibits ATP-dependent, MRP1-mediated LTC(4) uptake into membrane vesicles prepared from the MRP1… CONTINUE READING
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