Computational approaches in efflux pump inhibitors: current status and prospects

Drug Discov Today. 2020 Oct;25(10):1883-1890. doi: 10.1016/j.drudis.2020.07.011. Epub 2020 Jul 23.

Abstract

Treatment of bacterial infections is currently threatened by the development of antibiotic resistance and a poor pipeline of new antibiotics. Efflux pumps (EPs) are an integral part of the defense machinery of bacteria, preventing the entry of molecules, such as antibiotics, into the intracellular environment and resulting in antibiotic resistance. Therefore, research has focused on the discovery of novel EP inhibitors (EPIs), such as PAβN, D13-9001, and MBX2319. however, there are still no US Food and Drug Administration (FDA)-approved drugs targeting EPs because of the inadequate assimilation of the inhibitors. Here, we discuss the use of computational approaches for molecular mechanistic studies of EPIs to help direct future research.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology
  • Drug Development / methods
  • Drug Resistance, Bacterial
  • Humans
  • Membrane Transport Proteins / metabolism

Substances

  • Anti-Bacterial Agents
  • Membrane Transport Proteins