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

Article Details

Citation

Copy to clipboard

Montanari F, Ecker GF

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.

PubMed ID

25769815 [ View in PubMed

]

Abstract

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.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Ranolazine	P-glycoprotein 1	Protein	Humans	No	Substrate Inhibitor	Details