Prediction of drug-ABC-transporter interaction--Recent advances and future challenges

Adv Drug Deliv Rev. 2015 Jun 23;86:17-26. doi: 10.1016/j.addr.2015.03.001. Epub 2015 Mar 11.


With the discovery of P-glycoprotein (P-gp), it became evident that ABC-transporters play a vital role in bioavailability and toxicity of drugs. They prevent intracellular accumulation of toxic compounds, which renders them a major defense mechanism against xenotoxic compounds. Their expression in cells of all major barriers (intestine, blood-brain barrier, blood-placenta barrier) as well as in metabolic organs (liver, kidney) also explains their influence on the ADMET properties of drugs and drug candidates. Thus, in silico models for the prediction of the probability of a compound to interact with P-gp or analogous transporters are of high value in the early phase of the drug discovery process. Within this review, we highlight recent developments in the area, with a special focus on the molecular basis of drug-transporter interaction. In addition, with the recent availability of X-ray structures of several ABC-transporters, also structure-based design methods have been applied and will be addressed.

Keywords: ABC transporters; Bioassays; Computational models; Machine learning; Pharmacophore modeling; Transport inhibition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Humans
  • Ligands
  • Models, Biological*
  • Molecular Structure
  • Pharmaceutical Preparations / metabolism*


  • ATP-Binding Cassette Transporters
  • Ligands
  • Pharmaceutical Preparations