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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
10:43

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein

Published on: December 3, 2010

The medicinal chemistry of multidrug resistance (MDR) reversing drugs

E Teodori1, S Dei, S Scapecchi

  • 1Dipartimento di Scienze Farmaceutiche, Universita' di Firenze, Florence, Italy.

Farmaco (Societa Chimica Italiana : 1989)
|June 13, 2002
PubMed

Insights

Multidrug resistance (MDR) in cancer cells involves drug efflux pumps like P-glycoprotein. New chemosensitizers are being developed to overcome MDR with fewer side effects.

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Pharmacology

Background:

  • Multidrug resistance (MDR) is a major challenge in cancer chemotherapy, where cancer cells become resistant to structurally unrelated drugs.
  • Classical MDR is often mediated by ATP-dependent efflux pumps, such as P-glycoprotein (Pgp) and multidrug resistance protein 1 (MRP1), which reduce intracellular drug concentrations.
  • These transporters, belonging to the ABC superfamily, also play crucial physiological roles in non-tumoural tissues and prokaryotes.

Purpose of the Study:

  • To review the medicinal chemistry of multidrug resistance (MDR) reversers, focusing on agents currently in development.
  • To highlight the evolution of MDR modulators from early compounds with significant side effects to newer, more potent, and selective agents.
  • To discuss the development of chemosensitizers for treating resistant tumors.

Main Methods:

  • Literature review of medicinal chemistry efforts in developing MDR reversers.
  • Analysis of drug development strategies for novel chemosensitizers.
  • Focus on drugs currently undergoing clinical evaluation for resistant tumors.

Main Results:

  • Early MDR modulators often had dose-limiting side effects due to their own pharmacological actions.
  • Significant progress has been made in developing more potent and selective MDR reversing agents.
  • Several novel chemosensitizers are in clinical trials for treating resistant cancers.

Conclusions:

  • Medicinal chemistry plays a vital role in designing effective MDR reversers.
  • The development of selective chemosensitizers aims to improve cancer treatment outcomes by overcoming drug resistance.
  • Ongoing research focuses on optimizing potency, selectivity, and pharmacokinetics of MDR modulators for clinical application.

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