Protein Profiles: Drug Transporters

Pharma IQ

Drug transporters are vitally important to understanding pharmacokinetics of a drug and for assessing the possibility of drug-drug interactions. Many were originally of interest at their bacterial homologs mediated anti-bacterial resistance by pumping the drug out of the cell.

In the development of new drugs, there are currently seven classes of transporters which are clinically relevant and when developing a new small molecule drug, regulators require that these seven are studied for any effects on drug safety. The International Transporters Consortium has now recommended that five new transporter classes are added to these studies. With this in mind we thought we’d take a brief look at these proteins to examine who the newest clinically relevant drug transporters are.

MATEs- Multi antimicrobial extrusion protein. Identified in 2005, these antiporter proteins “play an important role in the renal and biliary elimination of various drugs including metformin”[1]. MATE1 is important in transporting anorganic cations into the bile. In the kidney, both MATE1 and MATE2-K are involved in transporting these cations into urine. [2] MATE1 is predicted to have 12 transmembrane helices.

MRP2- Multidrug Resistance associated Protein-2. A member of the ABC superfamily, in humans they are involved in the transport of drugs out of the kidney into urine in the proximal tubules. Some drugs can inhibit the MRP2 transporter causing build-up of the drug in the cell and potentially Fanconi Syndrome.

BSEP- Bile Salt Export Pump. This transporter is the primary transporter of bile acid which is essential for several important steps in the digestive process.  [3] This protein may also play a role in drug-induced hyperbilirubinemia.[4] Research has shown that inhibition of this transporter correlates with cholestatic drug-induced liver injury in humans [5]

PepT1- Peptide Transporter 1. PepT1 is a cotransporter which works to reabsorb peptides in the kidney, absorb dietary nitrogen in the kidneys and plays a role in initiating the innate immune response. As Dr Simon Newstead stated in a recent interview with Pharma IQ, there is increasing interest in taking advantage of these transporters to increase absorbtion of antibiotics by administration of peptide pro-drugs.

ENT1- Equilibrative nucleoside transporter 1. A reuptake transporter which reabsorbs nucleosides in an equilibrative manner as opposed to concentrative. ENT1 is known to affect the activity of cytarabine on leukaemia cells.[6]


 [[1] Kim, T., Kim, K., Park, H., Kim, S. and Choi, J. 2013. Identification and functional characterization of novel MATE1 genetic variations in Koreans.. pp. 334-40

[2] Motohashi, H. and Inui, K. 2013. Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K.. Mol Aspects Med., pp. 661-8.

[3] Soroka, C. and Boyer, J. 2013. Biosynthesis and trafficking of the bile salt export pump, BSEP: Therapeutic implications of BSEP mutations.. Mol Aspects Med.

[4] Chang, J., Plise, E., Cheong, J., Ho, Q. and Lin, M. 2013. Evaluating the In Vitro Inhibition of UGT1A1, OATP1B1, OATP1B3, MRP2, and BSEP in Predicting Drug-Induced Hyperbilirubinemia.. Mol Pharm..

[5] Dawson, S., Stahl, S., Paul, N., Barber, J. and Kenna, J. 2013. In vitro inhibition of the bile salt export pump correlates with risk of cholestatic drug-induced liver injury in humans.. Drug Metab Dispos.

[6] Macanas-Picard, P. et al. 2012. Bone marrow stromal cells modulate mouse ENT1 activity and protect leukemia cells from cytarabine induced apoptosis.. PLoS One.