Inhibitors of ABC transporters and biophysical methods to study their activity

Area of Science:

• Biochemistry
• Molecular Biology
• Pharmacology

Background:

• Multidrug resistance (MDR) in cancer is often mediated by ATP-binding cassette (ABC) transporters that efflux therapeutic drugs.
• Increased drug dosage is insufficient to overcome MDR, necessitating a deeper understanding of ABC transporter mechanisms.
• ABC transporters utilize ATP hydrolysis for energy to pump drugs out of cancer cells.

Purpose of the Study:

• To review known inhibitors of ABC proteins involved in multidrug resistance.
• To describe biophysical methods for measuring the activity of ABC transporters.
• To provide insights into overcoming multidrug resistance through understanding ABC transporter function.

Main Methods:

• Literature review of ABC transporter inhibitors.
• Description of biophysical techniques, including fluorescent dyes, for assessing efflux pump activity.
• Utilizing yeast Saccharomyces cerevisiae as a model organism with PDR pumps analogous to mammalian MDR proteins.

Main Results:

• Identification of various inhibitors targeting ABC proteins.
• Demonstration of the suitability of biophysical methods for quantifying efflux pump activity.
• Highlighting the role of yeast PDR pumps as valuable models for mammalian MDR proteins.

Conclusions:

• Understanding ABC transporter structure and function is crucial for developing strategies against multidrug resistance.
• Inhibitors of ABC transporters, combined with anticancer drugs, offer a potential therapeutic approach.
• Biophysical methods provide effective tools for studying ABC transporter activity and evaluating potential inhibitors.