Tricyclic isoxazoles are novel inhibitors of the multidrug resistance protein (MRP1).
@article{Norman2002TricyclicIA, 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}, year={2002}, volume={12 6}, pages={ 883-6 } }
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
Topics from this paper
52 Citations
Cyclohexyl-linked tricyclic isoxazoles are potent and selective modulators of the multidrug resistance protein (MRP1).
- Chemistry, Medicine
- Bioorganic & medicinal chemistry letters
- 2005
- 32
Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters.
- Biology, Medicine
- Biochemical pharmacology
- 2004
- 32
9-Deazapurines as Broad-Spectrum Inhibitors of the ABC Transport Proteins P-Glycoprotein, Multidrug Resistance-Associated Protein 1, and Breast Cancer Resistance Protein.
- Chemistry, Medicine
- Journal of medicinal chemistry
- 2017
- 20
Synthesis and multidrug resistance reversal activity of 1,2-disubstituted tetrahydroisoquinoline derivatives.
- Biology, Medicine
- Anticancer research
- 2004
- 9
Small‐molecule inhibitors of multidrug resistance‐associated protein 1 and related processes: A historic approach and recent advances
- Biology, Medicine
- Medicinal research reviews
- 2019
- 16
Anticancer multidrug resistance mediated by MRP1: Recent advances in the discovery of reversal agents
- Biology, Medicine
- Medicinal research reviews
- 2005
- 99
MRP1 and its role in anticancer drug resistance
- Biology, Medicine
- Drug metabolism reviews
- 2015
- 62
- Highly Influenced
- PDF
Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2.
- Chemistry, Medicine
- Biochemical pharmacology
- 2005
- 158
Modulation of multidrug resistance protein 1 (MRP1/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives.
- Chemistry, Medicine
- Journal of medicinal chemistry
- 2009
- 67
Multiple flavonoid-binding sites within multidrug resistance protein MRP1
- Biology, Medicine
- Cellular and Molecular Life Sciences CMLS
- 2003
- 59
References
SHOWING 1-10 OF 14 REFERENCES
Selectivity of the multidrug resistance modulator, LY335979, for P-glycoprotein and effect on cytochrome P-450 activities.
- Biology, Medicine
- The Journal of pharmacology and experimental therapeutics
- 1999
- 169
- PDF
The MRP gene encodes an ATP-dependent export pump for leukotriene C4 and structurally related conjugates.
- Chemistry, Medicine
- The Journal of biological chemistry
- 1994
- 822
Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells.
- Biology, Medicine
- Cancer research
- 1994
- 799
- PDF
ATP-dependent 17-Estradiol 17-(-D-Glucuronide) Transport by Multidrug Resistance Protein (MRP)
- Biology
- The Journal of Biological Chemistry
- 1996
- 263
- PDF
Multidrug resistance protein (MRP)-mediated transport of leukotriene C4 and chemotherapeutic agents in membrane vesicles. Demonstration of glutathione-dependent vincristine transport.
- Chemistry, Medicine
- The Journal of biological chemistry
- 1996
- 520
Reversal of resistance in multidrug resistance protein (MRP1)-overexpressing cells by LY329146.
- Chemistry, Medicine
- Bioorganic & medicinal chemistry letters
- 1999
- 26
Mechanisms of multidrug resistance in HL60 cells. Analysis of resistance associated membrane proteins and levels of mdr gene expression.
- Biology, Medicine
- Biochemical pharmacology
- 1989
- 146
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line.
- Biology, Medicine
- Science
- 1992
- 2,935
ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein.
- Biology, Medicine
- Cancer research
- 1994
- 433