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Pharmaceutics 2018, 10(3), 127; https://doi.org/10.3390/pharmaceutics10030127

The Effects of Synthetically Modified Natural Compounds on ABC Transporters

1
School of Science, Auckland University of Technology, Auckland 1010, New Zealand
2
Translational Genomics Research Institute, Phoenix, AZ 85004, USA
3
AUT-Roche Diagnostics Laboratory, Auckland 1010, New Zealand
4
School of Interprofessional Health Studies, Auckland University of Technology, Auckland 0627, New Zealand
5
College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518061, China
6
College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi’an 710062, China
7
Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland 1023, New Zealand
8
Auckland Cancer Society Research Centre, University of Auckland, Auckland 1023, New Zealand
*
Author to whom correspondence should be addressed.
Received: 29 June 2018 / Revised: 3 August 2018 / Accepted: 7 August 2018 / Published: 9 August 2018
(This article belongs to the Special Issue ABC Transporter-Mediated Drug Disposition)
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Abstract

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. View Full-Text
Keywords: ABC transporter; drug disposition; multidrug resistance; P-glycoprotein (P-gp); breast cancer resistant protein (BCRP); multidrug resistance-associated proteins (MRPs) ABC transporter; drug disposition; multidrug resistance; P-glycoprotein (P-gp); breast cancer resistant protein (BCRP); multidrug resistance-associated proteins (MRPs)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Dantzic, D.; Noel, P.; Merien, F.; Liu, D.-X.; Lu, J.; Han, H.; McKeage, M.J.; Li, Y. The Effects of Synthetically Modified Natural Compounds on ABC Transporters. Pharmaceutics 2018, 10, 127.

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