Journal
CHINESE JOURNAL OF CANCER
Volume 31, Issue 2, Pages 58-72Publisher
SUN YAT SEN UNIV MED SCI WHO
DOI: 10.5732/cjc.011.10329
Keywords
Multidrug resistance protein (MRP); multidrug resistance (MDR); ABC transporter; chemotherapy
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Funding
- NIH [1R15CA143701]
- St. John's University Seed Grant [579-1110-7002]
- Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University
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Multidrug resistance proteins (MRPs) are members of the C family of a group of proteins named ATP-binding cassette (ABC) transporters. These ABC transporters together form the largest branch of proteins within the human body. The MRP family comprises of 13 members, of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell. They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione (GSH), glucuronate, or sulphate. In addition, MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH. Collectively, MRPs can transport drugs that differ structurally and mechanistically, including natural anticancer drugs, nucleoside analogs, antimetabolites, and tyrosine kinase inhibitors. Many of these MRPs transport physiologically important anions such as leukotriene C4, bilirubin glucuronide, and cyclic nucleotides. This review focuses mainly on the physiological functions, cellular resistance characteristics, and probable in vivo role of MRP1 to MRP9.
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