The Effects of Synthetically Modified Natural Compounds on ABC Transporters

Pharmaceutics

MarkJ. McKeage¹  Fabrice Merien²  Dong-Xu Liu²  Jun Lu²  Daniel Dantzic²  Yan Li²  Pawan Noel³  Haiyong Han³ 

[1] Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland 1023, New Zealand;School of Science, Auckland University of Technology, Auckland 1010, New Zealand;Translational Genomics Research Institute, Phoenix, AZ 85004, USA;

关键词: ABC transporter;    drug disposition;    multidrug resistance;    P-glycoprotein (P-gp);    breast cancer resistant protein (BCRP);    multidrug resistance-associated proteins (MRPs);   

DOI  :  10.3390/pharmaceutics10030127

来源: DOAJ

【 摘 要 】

Multidrug resistance (MDR) is a major hurdle which must be overcome to effectively treat cancer. ATP-binding cassette transporters (ABC transporters) play pivotal roles in drug absorption and disposition, and overexpression of ABC transporters has been shown to attenuate cellular/tissue drug accumulation and thus increase MDR across a variety of cancers. Overcoming MDR is one desired approach to improving the survival rate of patients. To date, a number of modulators have been identified which block the function and/or decrease the expression of ABC transporters, thereby restoring the efficacy of a range of anticancer drugs. However, clinical MDR reversal agents have thus far proven ineffective and/or toxic. The need for new, effective, well-tolerated and nontoxic compounds has led to the development of natural compounds and their derivatives to ameliorate MDR. This review evaluates whether synthetically modifying natural compounds is a viable strategy to generate potent, nontoxic, ABC transporter inhibitors which may potentially reverse MDR.

【 授权许可】

Unknown